The optimal ZnCo2O4 HTNs, as a representative substance applied in supercapacitors as the positive electrode, delivers a high specific capacity of 181 C g−1 at a current density of 0.5 A g−1, an excellent rate performance of 75.14% and a superior capacity retention of 97.42% after 10 000 cycles. Furthermore, an asymmetric supercapacitor assembled from ZnCo2O4 HTNs and active carbon also shows a stable and ultrahigh cycling stability with 95.38% of its original capacity after 20 000 cycle tests.Uniform one-dimensional metal oxide hollow tubular nanofibers (HTNs) have been controllably prepared using a calcination strategy using electrospun polymer nanofibers as soft templates and zeolitic imidazolate framework nanoparticles as precursors. Utilizing the general synthesis method, the ZnO HTNs, Co Uniform metal oxides hollow tubular nanofibers have been controllably prepared by calcination strategy using electrospun polymer nanofibers as soft templates and zeolitic imidazolate framework nanoparticles as precursors for long-life supercapacitor. Therefore, the study of environment friendly energy sources and storage devices has become a hot topic in the present society.18–20 Especially, one-dimensional (1D) hollow tubular nanofibers (HTNs) structures contain merits including high surface area, low density and functional thin shell endowing them adequate potential to be applied in energy storage field.21,22 Nevertheless, the synthesis process of hollow tubular structures usually need hard templates or relatively complicated synthesis steps, which usually creates additional consumption.23–26 Therefore, it is highly desirable to explore facile and controllable synthesis strategy to form electrode materials with outstanding cycle performance. It is worth to note that electrospinning technique is a famous strategy for manufacturing nano-scale fibers with the uniform size, large surface area and highly controllability, and is applied to many fields such as lithium ion battery, solar cells and SCs.27–30 Some researchers have prepared 1D composite nanofibers by mixed the polymer solutions and electrochemical active materials, others have used the electrospun carbon nanofibers as a hard template to make structural fibers.23,29Hollow tubular structure materials have been studied extensively as a class of the structural electrodes materials in recent times.3O4 and ZnCo2O4). By combining electrospinning technology and calcination process, the metal oxides HTNs are obtained by using polymer nanofibers as the soft template and zeolitic imidazolate framework (ZIF) as the precursor and metal source. Such uniform nanofibers can provide large specific surface areas and a shorter ions transport path. Furthermore, the excellent hollow tubular structure not only provides sufficient active sites for electrochemical reaction, but also effectively resists changes in the volume of the material during cycling process. For example, the ZnCo2O4 HTNs display a high specific capacity of 181 C g−1 and an outstanding cycling performance of 97.42% after 10 000 cycles as the positive electrode for SCs. Moreover, an asymmetric supercapacitor assembled by ZnCo2O4 HTNs and active carbon (AC) also shows a desirable electrochemical performance .Herein, we report a simple and effective method to prepare metal oxides HTNs  and 4 mmol of cobalt acetate tetrahydrate (Co(Ac)2·4H2O) in 5 ml of dimethylformamide (DMF) with stirring for 12 h. The high voltage, flow rate, and distance between spinneret-to-collector are set as 20 kV, 0.8 ml min−1 and 15 cm, respectively.The electrospinning solution is prepared by dissolving 0.45 g of polyacrylonitrile (PAN), 2 mmol of zinc acetate dihydrate (Zn(Ac)2/Co(Ac)2 composite nanofibers into the solution. Then, the mixture is kept at room temperature for 24 h, the obtained core–shell PAN@ZnCo-ZIF composite nanofibers are washed by ethanol for several times.In a typical synthesis, 2.5 mmol of 2-methylimidazole (2-MIM) is dissolved into 60 ml of ethanol, followed by the addition of 10 mg of the PAN@Zn(Ac)−1 to obtain the ZnCo2O4 hollow tubular nanofibers. For comparision, the ZnO HTNs and Co3O4 HTNs are prepared in a similar process but only with the addition of Zn2+ or Co2+ ions.The above PAN@ZnCo-ZIF core–shell nanofibers are thermal annealed in air at 600 °C for 2 h with a heating rate of 2 °C minThe morphology and composition of the materials are characterized by scan electron microscopy , transmission electron microscopy  equipped with energy-dispersive X-ray spectroscope (EDS) detectors and high-resolution TEM (HRTEM). X-ray diffraction  with Cu-Kα radiation measurements are carried out to examine the crystal phase of the samples. X-ray photoelectron spectrometer  is used to obtain the photoelectrically spectroscopy. Thermogravimetric analysis  is carried out to verify the temperature of calcination. Nitrogen adsorption–desorption measurements are implemented on a Quadrachrome adsorption instrument  at 77 K. The pore-size distribution is calculated based on the Barrentt–Joyner–Halenda (BIH) method.2O4 HTNs and active carbon) are prepared by mixing the active materials (80%), acetylene black (10%), polyvinylidene fluoride  and 1 ml ethanol with a stirring process of 10 h to form a slurry. Then spreading the slurry onto Ni foam and the electrodes are dried at 80 °C for 12 h under vacuum. The loading mass of ZnCo2O4 HTNs and active carbon is about 2.0 mg cm−2.The working electrodes  as the reference electrode in an aqueous KOH electrolyte (2.0 M) by means of an electrochemical workstation (CHI 660D) at room temperature.C, C g−1) is calculated based on the following formula 31I (A), Δt (s) and m (g) represent the discharge current, discharge time and the mass of the active materials, respectively.The specific capacity  and ΔV− represent the potential window of the positive and negative electrodes.The asymmetric supercapacitor (ASC) device is assembled by using ZnCoE, W h kg−1) and power density  of the ASC device are calculated using the following 32V (V) and Δt (s) represent the potential window and the discharge time of the ASC device, respectively.The energy density 2 composite nanofibers can be transformed into PAN@ZIF core–shell nanofibers by immersed in ethanol solution containing 2-MIM ligand. Finally, after a calcination process under the air, the core layer of PAN is burned off, and at the same time, the shell layer of ZIF is also oxidized to metal oxides, the HTNs framework constructed by metal oxides nanoparticles derived from ZIF materials come to being. By executing this synthesis strategy, we have successfully prepared the ZnO HTNs, Co3O4 HTNs and ZnCo2O4 HTNs, which means the current strategy is general, simple and effective, provides a guiding method for preparation of metal oxides hollow tubular nanofibers structure.The preparation method of metal oxides HTNs is shown in 2O4 HTNs are described as a typical sample. The smooth and flexible PAN@Zn(Ac)2/Co(Ac)2 composite nanofibers with a diameter of 200 ± 50 nm , ZIF nanoparticles grow on the surface of composite nanofibers uniformly, forming the PAN@ZnCo-ZIF core–shell nanofibers  image  study, the distinct diffraction ring confirms the crystal nature of the product effectively.35,36 In addition, the elemental mapping test further proves the homogeneous distribution of Zn, Co and O elements in the whole fibers  image , and it e fibers . The nitg Fig. S3. The mes1/2 (1042.76 eV and 1044.3 eV) and Zn 2p3/2 (1019.7 eV and 1021.23 eV), suggesting the valence of Zn in the sample is +2 , hydroxyl group  and adsorption water .40,41 This study result further demonstrates the successful preparation of ZnCo2O4.The valence states of the elements in the sample surfaces are revealed by XPS analysis. The survey image suggests the co-existence of Zn, Co and O elements , which ile is +2 .37 For tof Co 2p , two spiee peaks , metal–o2 and PAN@Co(Ac)2 composite nanofibers are synthesized precisely by adjusting the kind of the adding metal element, after a solvent method treatment in room temperature, the PAN@ZIF-8 and PAN@ZIF-67 core–shell nanofibers are prepared, which is similar to the PAN@ZnCo-ZIF.42,43 Under the calcination process, the corresponding HTNs of ZnO and Co3O4 are synthesized resoundingly  strongly support the successful preparation of the ZnO HTNs and Co3O4 HTNs 3O4 HTNs and ZnCo2O4 HTNs, are studied by a three-electrode system in 2 M KOH electrolyte , and at the same time, the height of peak density was shifted gradually. This phenomenon may be caused by the diffusion of the ions inside the electrode materials. The separated redox peak implies the reversible faradaic reactions occurred between the electrode materials and the electrolyte. The galvanostatic charge/discharge (GCD) tests are carried out at different current density  and Co3O4 HTNs (128.9 C g−1) at a current density of 0.5 A g−1 . It is worth to note that for the ZnCo2O4 HTNs sample, the Zn atoms play a vital role in improving the conductivity and chemical stability of the electrode material.44 Relatively faradaic redox reactions are the following 46The electrochemical behaviors of ZnO HTNs, Co Fig. S7a, the redectively . This co.5 A g−1 . In addi−1, we can probe into the mechanisms of charge storage. The relationship between peak current (i) and scan rate (v) can be explored based on the power law a is constant, b is the power law exponent and it's also the slope of the linear plot of log(i) against log(v). In general, when b = 0.5, a diffusion-controlled contribution is happened, while b = 1 indicates a capacitive-controlled process. For ZnCo2O4 HTNs, the b values of cathodic is 0.718 , and the radius of a semicircle at high frequency range was relevant to the interface charge transfer resistance (Rct). Compared to the Co3O4 HTNs (Rct = 0.1012 Ω) and ZnCo2O4 HTNs (Rct = 0.01686 Ω) curve, the ZnO HTNs (Rct = 0.01281 Ω) exhibit the smallest semicircle and biggest slope, suggesting that ZnO HTNs have the strongest charge transfer impetus at the interface of electrode/electrolyte. Moreover, for the EIS curves intersection with the X-axis corresponding to the equivalent series resistance (Rs), ZnCo2O4 HTNs (0.9218 Ω) curve has a minimum value contrast with ZnO HTNs (1.112 Ω) and Co3O4 HTNs (1.508 Ω). This result further proofs the crucial impact of Zn atom for improving the material conduction. The cycling stability measurements are performed at 10 A g−1 for 10 000 GCD cycles. For the ZnCo2O4 HTNs electrode, it shows a particularly low capacity loss about 2.58% after cyclic testing (3O4 HTNs (83.33%) also have an outstanding cycling performance. This result is highly comparable in the respect of specific capacity, and this work has the longest cycling performance with relevant materials reported previously  tests are used to assess the charge transfer kinetics of electrodes in the frequency range from 0.01 Hz to 100 kHz . At low  testing . It is i Table S1.2O4 HTNs as a specimen to design an asymmetric supercapacitor (ASC), using the ZnCo2O4 HTNs and the active carbon (AC) as positive and negative electrode, respectively. For the electrochemical performance of AC electrode in three-electrode system ,48 hollow ZnCo2O4 microspheres (12.62 W h kg−1 at 920.8 W kg−1),49 ZnCo2O4 ultra-thin curved sheets (10.2 W h kg−1 at 4250 W kg−1),50 ZnCo2O4/H:ZnO NRs (3.75677 W h kg−1 at 653.34 W kg−1).51In order to investigate the practical application of metal oxides HTNs, we choose the ZnCo Fig. S11, the appbehavior . After c10 A g−1 , which m g−1 (−1 . For theFig. S12d, which pSuch a prominent electrochemical property of transition metal oxides HTNs mainly put down to the excellent structural and compositional nature. The uniform nanofibers feature can provide a shorter diffusion path, the addition of zinc also greatly increase the chemical stability of electrode materials. Besides, the large specific surface area from the hollow structure can ensure the sufficient content between electrode and electrolyte, which resulting in a high rate capability. Specifically, the 1D tubular structure can store enough electrolytes, reduce the volume change of electrode materials during circulation, thus generating an outstanding cycle performance.2O4 HTNs deliver a desirable electrochemical performance, a high specific capacity of 181 C g−1 at the current density of 0.5 A g−1 with a capacity retention of 97.42% after 10 000 cycles when applied in SCs as the positive electrode. The ASC assembled from ZnCo2O4 HTNs and active carbon also shows a stable and ultrahigh cycling stability with 95.38% of original capacity after 20 000 cycle tests. Therefore, this synthetic strategy offers a direction for the study of hollow tubular nanofibers structure and long cycle life electrode materials.In summary, we reported a simple and controllable calcination approach to prepare the transition metal oxides HTNs, utilizing electrospun polymer nanofibers as soft template as well as using ZIF nanoparticles as the metal sources. A representative substance, ZnCoThere are no conflicts to declare.RA-010-D0RA01844A-s001


DANCR is an RNA gene located on chr4. This gene has several splice variants. Up-regulation of DANCR has been reported in many types of cancers. This lncRNA is mainly located in the cytoplasm and regulates genes expression at post-transcriptional level. In fact, it acts as a molecular sponge for a variety of miRNAs, including miR-874-3P, miR-335, miR-149, miR-4319, miR-758-3p, miR-216a-5p, miR-874-3p, miR-33a-5p, miR-335-5p, miR-145-3p, miR-665, miR-345-5p and miR-125b-5p. DANCR also regulates activity of PI3K/AKT/NF-κB, Wnt/β-catenin, ERK/SMAD, MAPK, IL-6/JAK1/STAT3, Smad2/3, p53, FAK/PI3K/AKT/GSK3β/Snail pathways. In the current narrative review article, we summarize the roles of DANCR in the carcinogenesis, with an especial emphasis on its role in the development of osteosarcoma and lung, liver, pancreatic and colorectal cancers. DANCR (Differentiation Antagonizing Non-Protein Coding RNA) is an RNA gene located on chr4: 52,712,257–52,723,623, plus strand. It has a size of 11,367 bases. This gene has 14 splice variants with sizes ranging from 272 bp (DANCR-207) to 6065 bp (DANCR-203), all of them being categorized as long non-coding RNA (lncRNA). This lncRNA has been regarded as a cancer-associated lncRNA, since its up-regulation has been reported in several cancer types in association with enhancement of cell proliferation and malignant properties [Up-regulation of DANCR has been shown to upsurge proliferation, migratory propensity, and invasiveness of osteosarcoma cells. From a functional aspect, DANCR promotes progression of osteosarcoma through induction of cancer stem cells properties. DANCR up-regulates expression of AXL through sequestering miR-33a-5p. Further, DANCR enhances activity of AXL/Akt pathway. Cumulatively, DANCR is an important regulator of osteosarcoma progression . AnotherIn bladder cancer cells, DANCR silencing has inhibited proliferation, migratory potential and invasion. DANCR has been shown to target miR-335/VEGF-C. miR-335 mimics could promote proliferation and invasive properties bladder cancer cells. In contrast, up-regulation of DANCR removes the effect of miR-335 mimics on these cells . In addiIn lung cancer cells, DANCR expression levels have been negatively correlated with levels of miR-216a . AnotherHepatocellular carcinoma is another type of cancer in which DANCR has an important effect. Up-regulation of DANCR in these cells has been associated with down-regulation of miR-125b-5p. DANCR silencing or miR-125b-5p mimics could reduce cell cycle progression in HepG2 or Huh-7 cells, while promoting cell apoptosis. Both interventions could also inhibit migratory potential and invasiveness of these cells. Mechanistically, DANCR facilitates progression of this cancer through sponging miR-125b-5p and activating MAPK pathway . DANCR cIn colorectal cancer cells, DANCR has been shown to affect activity of miR-125b-5p/HK2 axis to induce resistance to cisplatin through induction of anaerobic glycolysis . In addiIn pancreatic cancer cells, DANCR regulates expression of miR-33b to promote proliferation and metastatic abilities . MoreoveExpression of DANCR has been found to be high in cisplatin-resistant gastric cancer cells. However, siRNA-mediated silencing of this lncRNA in SGC7901/DDP and BGC823/DDP cells has led to significant decrease in their survival and induction of apoptosis. Furthermore, DANCR up-regulation could up-regulate expression levels of MDR1 and MRP1 in cisplatin resistant gastric cancer cells . AnotherTable Up-regulation of DANCR in osteosarcoma cells has been shown to promote xenograft tumor growth and lung metastases . CriticaExpression of DANCR has been constantly enhanced in osteosarcoma samples, and its up-regulation has been positively associated with size of tumors and their metastatic ability. In fact, it is regarded as an independent poor prognostic factor for osteosarcoma. Besides, in patient samples, DANCR expression has been positively correlated with AXL levels and negatively correlated with expression levels of miR-33a-5p . DANCR oDANCR is regarded as an oncogene in almost all types of cancers. All conducted studies have indicated up-regulation of DANCR in cancer tissues/cell lines except for a single study in renal cell carcinoma . MoreoveOver-expression of DANCR has also been associated with resistance to anti-cancer agents such as cytarabine, sorafenib, cisplatin and docetaxel. These findings indicate that DANCR-targeting therapies might affect response of cancer cells to a wide array of drugs, possibly conquering multidrug resistance.DANCR has also been shown to possess appropriate diagnostic power to differentiate patients with liver cancer from healthy persons or those with non-malignant liver disorders . Since tTens of tumor suppressor miRNAs have been shown to be sponged by DANCR, leading to release of miRNA targets from their inhibitory effects. DANCR can also regulate activity of several important cancer-related pathways such as PI3K/AKT/NF-κB, Wnt/β-catenin, ERK/SMAD, MAPK, IL-6/JAK1/STAT3, Smad2/3, p53, FAK/PI3K/AKT/GSK3β/Snail pathways. Since several signaling pathways are influenced by DANCR, drugs targeting this lncRNA are expected to affect numerous aspects of carcinogenesis, thus being effective in treatment of a wide range of cancers with different biological behaviors.In addition, DANCR has interactions with a number of proteins including CTNNB1, RXRA, EZH2 and PRC2. Most importantly, interaction of DANCR with proteins that influence epigenetic marks shows the importance of DANCR in the regulation of gene expression.DANCR gene and susceptibility to cancer have not been appraised yet. Thus, future investigations should focus on these aspects. High throughput sequencing techniques could facilitate answering to these questions in near future.Although several expression assays have assessed expression levels of DANCR in biological samples obtained from different types of cancers, the underlying cause of dysregulation of DANCR in cancer has not been identified. In addition, the impacts of genomic variants on expression of this lncRNA and possible associations between single nucleotide polymorphisms within


Antimicrobial resistance (AMR) has emerged as a major threat to the global healthcare economy during Coronavirus disease 2019 (COVID-19), especially in developing countries like Pakistan where the healthcare facilities are already substandard. To combat AMR, the World Health Organization (WHO) has taken several initiatives including the establishment of a sustainable Universal Health Coverage (UHC) system. The implementation of UHC could eliminate various factors that contribute to a high AMR rate including self-medication. Our commentary explores in depth the current UHC system in Pakistan and how UHC could be the answer to Pakistan’s AMR crisis. For decades developing countries have been plagued by increasing rates of antimicrobial resistance (AMR), a consequence of gross overconsumption of antibiotics . The incStaphylococcus aureus (MRSA) to be 49% and the resistant genes of Shigella, Klebsiella, Enterococcus, Acinetobacter, and E. coli were found to be 79%, 33%, 45%, 1.6% and 31% prevalent in the country, respectively [Pakistan’s healthcare system (HCS) is among those which are severely threatened by AMR as evidence shows that most bacteria have developed strong resistance to frequently used antibiotics in the country , renderiectively .The situation was made worse worldwide when the COVID-19 pandemic hit the globe, as the consumption of antibiotics increased by 23.3% during the pandemic  and an eThe high incidence of AMR in Pakistan can mostly be attributed to illiteracy that is prevalent throughout the country. Lack of awareness means that patients consume antibiotics as they see fit, their only concern being fast relief without any regard for the adverse effects of the antibiotics . StudiesSince AMR is a major burden on the global healthcare economy, WHO has launched several initiatives to combat its increase. In order to combat AMR, it is essential that an integrated One Health approach is taken that incorporates human health, animal health and the environment when considering the management of AMR . One of In recent years, Pakistan has taken several steps to establish UHC within the country. A health card has been introduced in two provinces, Khyber Pakhtunkhwa and Punjab, which has made healthcare affordable for even the underprivileged . The heaHealth cards should be available for citizens throughout the country, not just in specific provinces.The healthcare sector should collaborate with the media to spread maximum awareness regarding antibiotic resistance and how it can be prevented.All healthcare workers should be properly educated on AMR so they do not prescribe antibiotics unless absolutely necessary as trends show that the prescribing of medications by inadequately trained pharmacists and unlicensed practitioners only further worsens the AMR situation in the country .Free health clinics should be organized frequently in underdeveloped areas with detailed sessions on antibiotic resistance and how it is fuelled by self-medication.Pharmacies should not be authorized to sell antibiotics without a doctor’s prescription and should be mandated by the law to keep a track of all antimicrobials sold in order to accurately evaluate antibiotic consumption among the population so the AMR problem can be tackled accordingly.We suggest the following actions need to be considered for establishing UHC in the country and to uproot the AMR crisis:


A complementary metal-oxide-semiconductor (CMOS) image sensor fabricated with this novel epitaxial silicon wafer has a markedly reduced number of white spot defects, as determined by dark current spectroscopy (DCS). In addition, the amount of nickel impurities gettered in the CH2P-molecular-ion-implanted region of this CMOS image sensor is higher than that gettered in the C3H5-molecular-ion-implanted region; and this implanted region is formed by high-density black pointed defects and deactivated phosphorus after epitaxial growth. From the obtained results, the CH2P-molecular-ion-implanted region has two types of complexes acting as gettering sinks. One includes carbon-related complexes such as aggregated C–I, and the other includes phosphorus-related complexes such as P4–V. These complexes have a high binding energy to metallic impurities. Therefore, CH2P-molecular-ion-implanted epitaxial silicon wafers have a high gettering capability for metallic impurities and contribute to improving the device performance of CMOS image sensors. (This manuscript is an extension from a paper presented at the 6th IEEE Electron Devices Technology & Manufacturing Conference (EDTM 2022)).Using a new implantation technique with multielement molecular ions consisting of carbon, hydrogen, and phosphorus, namely, CH Complementary metal-oxide-semiconductor (CMOS) image sensors have been widely used not only for imaging using digital still cameras, smartphones, and others, but also for sensing in, for example, automobiles and security systems with the progress of the internet-of-things (IOT) society. Among them, three-dimensionally stacked back-side-illuminated CMOS image sensors (3D-CISs) products have been actively developed to achieve the desired characteristics, such as high resolution, high sensitivity, and high-speed imaging data processing . HoweverThe first important technological issue is metallic impurity contamination in the device active region during 3D-CIS fabrication processes, such as nickel silicide formation, electrode material deposition, and interconnection formation. Metallic impurity contamination tends to be enhanced because pixel dies are stacked on the signal processing circuit die using 3D-CIS integration technologies, such as Cu-through-silicon vias (Cu-TSVs) and Cu–Cu hybrid bonding ,5. MetalThe second important technological issue is the out-diffusion of oxygen impurities from a Czochralski (CZ) silicon substrate to the depletion layer of a photodiode in pixels . The oxyit) at the SiO2/Si interface formed in the deep trench isolation (DTI) region or at the bonding interface of 3D-CIS [it is the Si dangling bonds existing at the SiO2/Si interface , whib centers and reducing the Dit [2/Si interface owing to the multi-dielectric films acting as a barrier during FGA [Generally, low-temperature hydrogen forming gas annealing (FGA) at the back end of the line (BEOL) process is one of the methods of passivating P the Dit ,12,13. Hring FGA . Therefo3H5) molecular ion implantation technique [3H5-molecular-ion-implanted region has three characteristics that can resolve these technological issues, as shown in it utilizing the hydrogen trapped in the C3H5-ion-implanted region after epitaxial growth and to diffuse during the CMOS image sensor fabrication process [To realize this, we have developed an epitaxial silicon wafer with functional proximity gettering sinks introduced under the epitaxial silicon layer using the hydrocarbon  [Kurita and coworkers demonstrated that the three characteristics of Cpy (DCS) ,26. DCS py (DCS) ,27,28,292P molecular ions, with the aim of improving the gettering capability for metallic impurities among the three characteristics to further reduce the number of white spot defects in CMOS image sensors. As a gettering technique using phosphorus, high-density misfit dislocations and the P–V complex called E-centers are formed in the high-phosphorus-concentration region using thermally diffused phosphorus and phosphorus monomer ion implantation from the back surface of the silicon wafer; and they act as gettering sinks for metallic impurities [2P-molecular-ion-implanted epitaxial silicon wafer by comparing the number of white spot defects obtained by the DCS of the CMOS image sensor with a C3H5-molecular-ion-implanted epitaxial silicon wafer.Furthermore, we developed a new implantation technique with multielement molecular ions consisting of carbon, hydrogen, and phosphorus, namely, CHpurities ,31,32,3314/cm3, the carbon concentration was 4.7 × 1016/cm3, and the initial oxygen concentration was 14.5 × 1017/cm3 (old ASTM). The silicon wafer surface was implanted with CH2P molecular ions using CLARIS (Nissin Ion Equipment). The implantation conditions were an energy of 80 keV/molecule and a dose of 2.0 × 1014 ions/cm2 . The tilt and twist angles were both set to 0°. For the comparison of the number of white spot defects, C3H5-molecular-ion-implanted silicon wafers were prepared using the same energy (80 keV/molecule) and carbon dose (2.0 × 1014 atoms/cm2) as those for CH2P molecular ion implantation. After molecular ion implantation, the thickness of the epitaxial silicon layers deposited on the silicon surface by chemical vapor deposition was 5.0 µm. Subsequently, we fabricated a CMOS image sensor with four transistors in a pixel with a pinned photo diode using the CMOS device fabrication process.2P and C3H5 molecular ions by DCS. After that, these sensors and epitaxial silicon wafers were evaluated by the methods described below to confirm the difference in the number of white spot defects between the molecular-ion-implanted samples. The size and density of bulk microdefects (BMDs) were measured using a BMD analyzer . The concentration profiles of carbon, oxygen, phosphorus, and nickel in the depth direction were analyzed by secondary ion mass spectrometry (SIMS). In the case of analyzing the sensors, the surfaces of sensors were mechanically polished to a depth of about 0.5 µm before SIMS analysis. The defect distribution in each molecular ion implantation projection range was observed by transmission electron microscopy (TEM) . The amounts of molecular ion implantation defects were evaluated by room-temperature photoluminescence (RTPL) analysis . The morphology and the distribution of carbon and phosphorus in the CH2P-molecular-ion-implanted region at the atomic level were analyzed by laser-assisted atom probe tomography (L-ATP) . The L-ATP map and distribution of each element were analyzed using integrated visualization and analysis software (IVAS) from CAMECA . Finally, the carrier concentration distribution in the depth direction of CH2P-molecular-ion-implanted epitaxial silicon wafers were measured by spreading resistance analysis (SRA) .We measured the number of white spot defects in each image sensor implanted with CH2P- and C3H5-molecular-ion-implanted epitaxial silicon wafers measured at 60 °C. Our previous study already reported the dark current amount of CMOS image sensor dependence on, before, and after molecular ion implantation, such as C3H5 and CH3O molecular ions using DCS [sing DCS ,34. As adark) is forming the generation current (Igeneration), the surface generation current (Isurface), and the diffusion current (Idiffusion) (where Idark = dark current + white spot defects = Igeneration + Isurface + Idiffusion). The first two components are related to the process-induced defects, such as metallic impurity, deep-level defect concentration, SiO2/Si interface state defect concentration in the photo–diode space charge region, the transfer gate transistor in CMOS image sensor pixels, and last component is related to the energy band gap of intrinsic semiconductor silicon material using CMOS image sensor fabrication.Furthermore, it is well known that there are three components of dark current at the photo–diode junction in CMOS image sensor pixels. Dark current  of the DSC spectrum of the sensor with the CH defects .2P- and C3H5-molecular-ion-implanted region, as determined from the DCS spectra shown in 2P-molecular-ion-implanted region is 67% smaller than that in the sensors with the C3H5-molecular-ion-implnated region. We consider that the difference in the ratio of the amount of dark current depends on the metallic impurity concentration localized in the pixels. Thus, the analysis results focusing on the gettering capability of sensor wafers with the CH2P- and C3H5-molecular-ion-implanted regions are shown below to clarify the reduction in metallic impurities-related defects in the CMOS image sensor active region.2P- and C3H5-molecular-ion-implanted epitaxial silicon wafers. Both CMOS image sensors were fabricated using carbon-doped silicon wafer substrates with high densities of BMD acting as intrinsic gettering (IG) sites for metallic impurities [2P and C3H5 molecular ion implantation. This finding indicates that the reduction in the amount of dark current depends on molecular ion implantation conditions such as the molecular ion species.purities ,36. The 2P- and C3H5-molecular-ion-implantated region. The nickel impurities are gettered in each molecular-ion-implanted region formed under the epitaxial silicon layer. The amount of nickel impurities gettered in the CH2P-molecular-ion-implanted region is twice as high as that gettered in the C3H5-molecular-ion-implanted region, as shown 2P- and C3H5-molecular-ion-implanted epitaxial silicon wafers.2P- and C3H5-molecular ion-implanted regions in epitaxial silicon wafers. Both molecular-ion-implanted regions showed only black pointed defects, and no CH2P-molecular-ion-implantation-related specific defects were observed. However, the width of the distribution of black pointed defects in the CH2P-molecular-ion-implanted region is 60 nm, which is smaller than that of 100 nm in the C3H5-molecular-ion-implanted region. From these results, the densities of black pointed defects distributed in the CH2P- and C3H5-molecular-ion-implanted regions are 1.58 × 1016 and 6.67 × 1015/cm3, respectively. Thus, the black pointed defects in the CH2P-molecular-ion-implanted region distribute more locally than those in the C3H5- molecular-ion-implanted region.2P- and C3H5-molecular-ion-implanted regions. The penetration depth of 827 nm excitation is around 10 µm, which reflects the PL emission intensity in regions including the molecular-ion-implanted region. The interband transition emission peak intensity of silicon (1.12 eV) in both the CH2P- and C3H5-molecular-ion-implanted epitaxial silicon wafers is lower than that in the silicon wafer without molecular ion implantation. In addition, the intensity in the CH2P-molecular-ion-implanted epitaxial silicon wafer is lower than that in the C3H5-molecular-ion-implanted epitaxial silicon wafer. Thus, this experimental result indicates that the amount of implantation defects in the CH2P-molecular-ion-implanted region is higher than that in the C3H5-molecular-ion-implanted region.2P- and C3H5-molecular-ion-implanted regions after epitaxial growth. The concentrations of phosphorus and carbon are high in the CH2P-molecular-ion-implanted region after epitaxial growth. The depth profiles of carbon concentration in the CH2P-molecular-ion-implanted region show a higher peak and a sharper distribution than those in the C3H5-molecular-ion-implanted region. Oxygen impurities that diffuse to the epitaxial layer from the silicon substrate are trapped in both molecular-ion-implanted regions. Moreover, hydrogen is also trapped in both molecular-ion-implanted regions. The trapped hydrogen diffuses during the CMOS device fabrication process and acts as the passivation effect for Dit at the SiO2/Si interface [nterface ,22,23,242P- and C3H5-molecular-ion-implanted regions, which are obtained from 2P-molecular-ion-implanted region is higher than that in the C3H5-molecular-ion-implanted region after epitaxial growth regardless of the same carbon ion implantation dose. On the other hand, the concentration of oxygen impurities trapped in the CH2P-molecular-ion-implanted region is lower than that in the C3H5-molecular-ion-implanted region. These findings indicate that carbon localized in the CH2P-molecular-ion-implanted region has less interaction with oxygen, such as the formation of the C–O complex.2P-molecular-ion-implanted region after epitaxial growth. The acicular sample was machined parallel to the molecular-ion-implanted region, focusing on the black-pointed defects using a focused ion beam. 2P-molecular-ion-implnted region in the epitaxial silicon wafer determined by L-APT. Carbon atoms locally agglomerate in the molecular-ion-implanted region, and correspond to the black pointed defects observed in the TEM image. Carbon atoms probably delineate the aggregations of C–I clusters consisting of carbon and silicon self-interstitials. On the other hand, phosphorus atoms are uniformly distributed in the CH2P-molecular-ion-implanted region. Thus, from the 3D distribution map, it is considered that agglomerated carbon and phosphorus atoms are not synchronized and do not from complexes.2P-molecular-ion-implanted region after epitaxial growth obtained by SIMS and SRA. The peak concentration of phosphorus is 5.70 × 1018/cm3, whereas the peak carrier concentration is 7.37 × 1016/cm3. Thus, 98% phosphorus are deactivated. Previous studies showed that the deactivated phosphorus form complexes with vacancies such as Pn–V [ as Pn–V .2P-molecular-ion-implanted region is higher than that of the C3H5-molecular-ion-implanted region at the same carbon dose. From the evaluation results of each molecular-ion-implanted epitaxial silicon wafer, the characteristics of the CH2P-molecular-ion-implanted region are summarized as follows in comparison with those of the C3H5-molecular-ion-implanted region:(1)2P-molecular-ion-implanted region is higher than that in the C3H5-molecular-ion-implanted region;The density of black pointed defects distributed in the CH(2)2P-molecular-ion-implanted region is higher than that in the C3H5-molecular-ion-implanted region; andThe carbon concentration localized in the CH(3)n–V complexes and does not interact with carbon distributed at the same depth in the CH2P-molecular-ion-implanted region.Phosphorus is deactivated by forming PWe examine why the gettering capability of the CH2P- and C3H5-molecular-ion-implanted regions, as shown in 2P molecular ion implantation, carbon and phosphorus are implanted into the silicon surface; and at the same time, Frenkel pairs, such as interstitial silicon and vacancies, are generated. Then, the implanted carbon and phosphorus form a complex by reacting with the Frenkel pairs during epitaxial growth as follows:Si is interstitial silicon, P is phosphorus (n = 1–4), V is vacancy, and Sis is substitutional silicon. Carbon interacts with interstitial silicon to form a C–I complex, and phosphorus interacts with vacancies to form a Pn–V complex such as the P4–V complex, as shown in First, we describe the formation model of gettering sinks in the CH2P-molecular-ion-implanted region after epitaxial growth. On the other hand, the concentration of phosphorus is not high in the C3H5-molecular-ion- implanted region. Only the C–I complex is formed, and there is a high possibility that interstitial silicon and vacancies will be annihilated. Carbon that could not interact with interstitial silicon to form a C–I complex diffuses isotropically. Since the density of the C–I complex is low in the C3H5-molecular-ion-implanted region, the carbon concentration and black pointed defect density are low, as shown by SIMS and TEM. Therefore, the CH2P-molecular-ion-implanted region forms two types of complex, namely C–I and Pn–V, particularly for carbon and phosphorus.Pawlak and Duffy investigated the co-implantation of carbon and phosphorus monomer ions to suppress the enhanced phosphorus diffusion due to interact with interstitial silicon . They sh2P-molecular-ion-implanted region including C–I and Pn–V complexes for metallic impurities. Kurita and coworkers described that the gettering sinks in the C3H5-molecular-ion-implanted region originated from the black-pointed defects, which consist of carbon complexes such as agglomerated carbon–silicon self-interstitial clusters (C–I complex) [2P-molecular-ion-implanted region after epitaxial growth.Next, we consider the gettering capability of the CHcomplex) ,20,25,26complex) ,41,42. Mcomplex) ,44,45. Sn–V complex, Chan et al. developed gettering models of transition metals in the high-phosphorus-concentration region using DFT [n–V complex strongly binds to transition metals. In particular, the critical complex responsible for both phosphorus deactivation and metal gettering was identified to be the P4–V complex that most strongly binds transition metals, as shown As for the Psing DFT . Their r2P-molecular-ion-implanted epitaxial silicon wafer has a high gettering capability for metallic impurities because this implanted region is formed with high densities of agglomerated C–I complexes and P4–V complexes.Therefore, the CH2P-molecular-ion-implanted epitaxial silicon wafers. The amount of dark current in the CMOS image sensor with the CH2P-molecular-ion-implanted region was 67% lower than that of the CMOS image sensor with the C3H5-molecular-ion-implanted region with the same carbon dose. The CH2P-molecular-ion-implanted epitaxial silicon wafers show the same three characteristics as the C3H5-molecular-ion-implanted epitaxial silicon wafers that can resolve the three important technological issues of 3D-CISs. Among them, we specifically found the improvement of the gettering capability for metallic impurities. Focusing on the gettering capability of the CH2P-molecular-ion-implanted region, the amount of nickel impurities gettered in the CH2P-molecular-ion-implanted region was twice that gettered in the C3H5-molecular-ion-implanted region after the CMOS image sensor fabrication process. Regarding the characteristics of the CH2P-molecular-ion-implanted region, the carbon peak concentration and black pointed defect density are high, and phosphorus is mainly distributed in a deactivated state.We investigated the amount of dark current in CMOS image sensors fabricated with CH2P-molecular-ion-implanted region has two types of gettering sink, namely, the high-density C–I complex and P4–V complex aggregates, which have a high binding energy for metallic impurities. We believe that CH2P-molecular-ion-implanted epitaxial silicon wafers can contribute to the improvement of the performance of CMOS image sensors.Therefore, the CH


Structural racism and systemic health inequities have an overwhelming and deadly impact on racially and ethnically minoritized groups. Antimicrobial resistance (AMR) is widely considered a global public health threat, and concerns that minoritized groups are disproportionately affected are increasing. With the emergence and spread of AMR, novel therapies and prevention strategies are imperative. Coronavirus disease-19 (COVID-19) has highlighted stark imbalances in the hospitalization and death rates of minoritized individuals compared to their White counterparts, irrespective of the availability of targeted preventive therapies . Thus, dialogue regarding the utility of vaccines used prophylactically to decrease the number of infectious diseases cases and the historical lack of vaccine equity and uptake across minoritized groups is needed. All of these factors work in concert to increase the burden of AMR and ultimately health disparities within minoritized communities. Herein, we provide historical context pertaining to the impact of structural racism on healthcare inequities in the United States, we explore racial and ethnic disparities in AMR, and we discuss the intersection of racism, AMR, and vaccine equity. Lastly, we offer recommendations to mitigate the described inequities. These inequities are largely explained by racism and its effects on the lives of racially and ethnically minoritized individuals. More importantly, racism is independently related to all structural and social determinants of health. Structural factors, including the social separation of racial groups, through segregating policies, introduce environmental pollutants and infectious agents into minoritized communities. Additionally, racism within systems and policies, has resulted in lower rates of racial and ethnic minoritized groups that enroll or persist in higher education, limiting their employment opportunities and often translating to their lower socioeconomic status (SES). Inevitably, lower SES results in the reduced rates of health insurance and access to healthcare presently recognized across minoritized groups. Consequently, these individuals remain at increased risk for ill or unmanaged, acute, and chronic comorbidities. Infectious diseases are the second leading contributor to healthcare racial disparities, and the management of these morbidities often requires the use of antimicrobial therapy.Profound racial and ethnic disparities are deeply woven within the constructs of the US healthcare system. Antimicrobial resistance (AMR) is a public health threat and is widely considered a global pandemic. Furthermore, >100,000 people die from multidrug-resistant infections each year, positioning AMR as a leading cause of death. Notably, efforts to reduce AMR have included the development of national resistance surveillance databases and novel antimicrobial agents, the use of rapid diagnostics tools to quickly identify resistant organisms, and preventive therapeutics (vaccinations) to decrease disease burden. However, research that explores the racial disparities in antimicrobial usage and AMR across racial and ethnic groups is lacking.As infectious diseases have evolved and antimicrobial utilization has increased, the rapid propagation and development of advanced mechanisms of resistance have become a substantial clinical problem. Nonetheless, among the few studies that do report racial inequities in antimicrobial usage, those observed in intensive care units (ICU) bring forth several interesting factors. Notably, ICUs have been the focal points for the emergence and spread of AMR pathogens. Minoritized patients, specifically non-Hispanic Black individuals are less likely to receive timely antimicrobials for the treatment of severe morbidities including sepsis and septic shock in the ICU. Of note, the time to appropriate antimicrobial is independently associated with ICU patient mortality because the causative organisms isolated are often characterized by multidrug resistance. Moreover, the delay in appropriate therapy can result in the continued growth, propagation, and widespread dissemination of the resistant isolates.Currently there are conflicting reports on whether racial differences and/or disparities exist in antimicrobial usage, prescribing patterns, and resistance trends. When treated in hospitals with equal access to care, such as Veterans’ Affairs health systems, minoritized and non-Hispanic White patients have similar outcomes and access to essential treatments including antimicrobials, which may explain the lessened racial differences observed in AMR rates in this setting. However, minoritized patients are more likely to frequent hospitals in areas of lower SES, where funding and treatment resources are often minimal.Interestingly, hospital system and/or setting has been shown to be a factor in the quality of ICU care, and ultimately in the receipt of appropriate and timely antimicrobial therapy. These researchers reported that neighborhoods characterized by lower SES, and populated by minoritized individuals, had a higher incidence of invasive community-associated MRSA (CA-MRSA) infections.Although antimicrobial regimens for the treatment of CA-MRSA were not described in this study, other investigators have uncovered racial disparities in the management of skin and soft-tissue infections (SSTIs) caused by CA-MRSA. Non-Hispanic Black inpatients were more like to be prescribed clindamycin and not cefazolin therapy (the first-line option) than non-Hispanic White inpatients. This situation is troublesome because clindamycin requires frequent dosing and is associated with Clostridioides difficile infection (CDI) where racial disparities in incidence rates and clinical management have also been described. Even though data regarding income, SES, and insurance status or type were not collected, they are often factors in decisions regarding treatment selection.The lack of access to adequate resources and care, due to SES classification, resulting in disparities in AMR infection rates, has been described by See et al. Although SES and other sociodemographic factors were uncollected, the DMC is located in Detroit, Michigan, where Black individuals comprise >70% of the population and >30% of the city’s population is impoverished.Nonetheless, racial disparities in the incidence and prevalence of AMR infections and poor prescribing patterns for the prophylaxis and/or treatment of infectious morbidities is not specific to gram-positive organisms, adult patients, or inpatient treatment settings. In a retrospective study conducted at the Detroit Medical Center (DMC), investigators reported a greater number of carbapenem-resistant Enterobacteriaceae bloodstream infections in non-Hispanic Black patients than in non-Hispanic White patients. reported that non-Hispanic Black and Hispanic or Latino children were less likely to receive antimicrobials than their non-Hispanic White counterparts in the treatment of viral acute respiratory illnesses. These researchers linked this racial difference to potential provider implicit biases and to the historical overtreatment of non-Hispanic White patients due to their perceived increase in disease severity compared to minoritized patients. Nonetheless, antimicrobial prescribing practices for dentists in the United States are opposite those reported by Goyal et al. A retrospective study revealed that non-Hispanic Black and Hispanic or Latino patients respectively had 21% and 6% higher likelihoods of receiving antimicrobials following a dental visit compared to their non-Hispanic White counterparts. These researchers hypothesized that this was because the minoritized patients often required advanced procedures due to lack of regular access to dental care. Notably, several socioeconomic factors, including insurance status and SES, were identified as predictive markers of antimicrobial receipt. In sum, these studies show the impact that structural racism resulting in low SES, as well as provider biases, can have on AMR prescribing patterns and the potential for deleterious outcomes within minoritized communities.Of interest, Goyal et al This task force released a plan to improve antimicrobial use that included accelerating research on novel therapeutics and optimizing antimicrobial stewardship programs and requirements. Despite the plan’s focus on collecting and utilizing data to better understand resistance patterns, racial and ethnic disparities and associated outcomes are not recognized priorities.To mitigate the rising rates of AMR potentiated by the misuse of the antimicrobials, the federal government created a National Task Force on Combatting Antibiotic-Resistant Bacteria (CARB). Due to the limited supply, the allocation of the available novel agents is often limited to hospitals and institutions that can accommodate the costs. Consequently, the hospitals located in areas of lower SES, which minoritized patients are more likely to frequent, are less likely to be able to afford the heavily sought after but limited therapeutics.Formidable challenges remain in reaching the outlined goals and objectives of the plan within minoritized communities. Irrespective of the recognized need for novel therapeutics, new, innovative antimicrobials in the clinical pipeline are scarce, specifically those targeting extensively or multidrug-resistant organisms. This personnel includes trained infectious diseases physicians and pharmacists who can educate general providers and reduce the selection for AMR. These hospitals may also be less likely to have the ability to quickly identify prominent drug-resistant gene markers to optimize antimicrobial selections. Rapid diagnostic tools that are designed to quickly identify select and predetermined resistance genes have been shown to significantly enhance antimicrobial stewardship programs and improve AMR rates. Nevertheless, such technologies are typically associated with high costs; thus, the likelihood of their placement in hospitals largely populated by minoritized individuals is low.Additionally, poorly funded hospitals are also less likely to have the resources to employ the key stakeholders necessary for successful antimicrobial stewardship programs. Because they are used to prevent infectious disease, they are also vital to the prevention of subsequent secondary bacterial infections. Irrespective of the known role of vaccines in the prevention of respiratory infectious diseases and AMR, non-Hispanic Black, Hispanic/Latino, and Native American individuals are less likely to be immunized than White persons. As a result of this lack of uptake, the Centers for Disease Control (CDC) reports that these individuals are historically more likely to be hospitalized for extended intervals due to preventable respiratory infectious diseases. In part, this can be attributed to the systemic barriers that force minoritized individuals into multigeneration and high-density living arrangements, which can increase disease transmission. Also, minoritized individuals are more likely to have comorbidities that further complicate their disease severity and may compromise their humoral immune response functions. Furthermore, severe illness and complications, leading to prolonged hospital lengths of stay, have been linked to the development of AMR infections secondary to the primary infectious disease . More recently, hospitalizations due to severe coronavirus disease-19 (COVID-19) have been shown to result in the development of AMR infections. Despite the lack of data describing and quantifying the impact of secondary infections on patient outcomes, and whether racial differences exist, history attests to the likelihood of significant disparities.In addition to novel therapies and antimicrobial stewardship programs, CARB has also highlighted the important role that vaccinations have in decreasing AMR. Trustworthy messaging from racially concordant providers remains integral to increasing vaccine confidence and subsequently the willingness to be vaccinated. Nevertheless, for those individuals who are interested in being immunized, the inequitable distribution of the vaccines and lack of access within minoritized communities in the United States are clear limitations. Minoritized individuals are more likely to live in healthcare-provider and pharmacy deserts with limited locations where they can receive immunizations.The lack of vaccine uptake across minoritized groups for respiratory infectious diseases, specifically COVID-19, has been linked to several factors including hesitancy due to systemic racism and decades of medical mistreatment by the federal government as well as the vaccine inequities within minoritized communities. Language barriers and inaccurate translation on health department registration websites are also limitations to vaccination that widen the digital divide and its impact on equitable healthcare in the United States. Furthermore, minoritized individuals often rely on mass-transit modalities, but many of the available vaccination sites are in locations where these transportation mechanisms are not accessible. Additionally, vaccination schedules often conclude during early evening hours, which creates a barrier for essential working personnel.Furthermore, registration processes for the vaccines are largely Web based; however, minoritized communities are less likely than their White counterparts to have Internet access as well as e-mail accounts necessary for registration completion. Consequently, >1 year following the availability of the COVID-19 vaccines, >50% of minoritized individuals remain unvaccinated. Therefore, they are at heightened risk for severe COVID-19 and prolonged hospital visits for adequate treatment. Thus, the risk of AMR resistance, due to infection by a vaccine-preventable disease, remain ever present for minoritized individuals.Although strategies were rapidly developed at the start of the COVID-19 vaccination roll-out to address these limitations, including the establishment of low-barrier community-based vaccination clinics, many of these efforts have ceased as funding sources have evaporated.We must acknowledge that inequities in social determinants of health, as well as provider implicit and explicit biases, heavily influence antimicrobial prescribing patterns and the propagation of AMR. The lack of access to adequate healthcare is a consistent and significant contributor to the observed racial differences in prescribing patterns, resistance trends, and receipt of preventive therapies. It is imperative that healthcare professionals, identify their role in addressing and mitigating access limitations within minoritized communities. To effectively do this, they must identify, confront, and dismantle their own racial biases because they heavily influence clinical decision making. Healthcare professionals must also hold their colleagues accountable for any biased actions or attitudes that may negatively affect minoritized patients. The inclusion of this information and an exploration of the nuances in AMR within minoritized groups would be a worthwhile undertaking for researchers. The alteration of each goal and objective of the CARB national action plan to include the collection of specific race and ethnicity data to quantify differences is critical. As of March 2022, the Centers for Disease Control has expressed a commitment to facilitating the regular collection and reporting of health inequities related to key bacterial pathogens as well as other sociodemographic data  that would holistically identify mediating factors in the observed AMR inequities. Cross sharing of information and collaboration among these groups and the shared prioritization of identifying racial disparities in AMR will increase the likelihood of change.We must design research that accurately quantifies and characterizes existing racial differences and/or inequities in AMR. Race and ethnicity demographic data are often absent from AMR-related studies, despite recent federal efforts to improve the availability of this information.In vitro research that explores racial differences in the genotypes, phenotypes, or host immune factors that may contribute to AMR is needed as we navigate the best methods to equitably improve patient outcomes. Research quantifying the use of rapid diagnostics tools and their placement in hospitals that serve primarily minoritized communities is needed. Nonetheless, to adequately address AMR health equity gaps, it will be essential to provide and allocate federal funding to investigate researching and reporting opportunities.We must advocate for increased funding to advance AMR interventions and strategies within “minority-serving” institutions as well as the equitable pricing of novel technologies and therapeutics. Because minimal financial resources are a limitation to AMR management within minoritized communities, this additional funding would give hospitals in these areas the ability to employ specialized clinicians  to develop robust antimicrobial stewardship teams that will aid in promoting positive patient outcomes. Equitable pricing of rapid diagnostic tools would allow institutions to further optimize their stewardship programs. Additionally, antimicrobial pricing that unlinks revenues from sales would make novel therapies more accessible for institutions and would contribute to pharmacoequity. The role of immunizations in overcoming AMR should also be included in the education provided to communities to increase health literacy. Finally, interventions that include the placement of low-barrier vaccination clinics, alongside direct allocation and education, should be prioritized because they are substantially effective in increasing vaccination uptake and potentially reducing AMR disparities.We must recognize the role of vaccine equity in decreasing AMR within minoritized communities. Promoting vaccine equity and increased uptake among racially and ethnically minoritized groups is essential. Vaccines must be specifically allocated by federal, state, and local governments to vulnerable minoritized communities. Following allocation, developing innovative strategies to increase vaccine confidence will be important for raising immunization rates. Targeted education efforts in nontraditional community settings that include trusted faith and community leaders can be successful in changing attitudes surrounding vaccines across minoritized groups.Despite the limited, and in some ways, conflicting data that exist describing racial differences in AMR, it remains clear that socioeconomic and demographic factors, influenced by racism, affect the reported disparities Fig. . Thus, eIn conclusion, structural racism has a longstanding history in the United States, and it permeates almost every system, including health care. The AMR global pandemic has the potential to severely affect minoritized groups. Therefore, we must be intentional in identifying racial differences in antimicrobial usage, prescribing, and characterized genotypes and phenotypes to effectively create strategies to overcome the inequities. As cornerstones, these strategies should include initiatives to promote vaccine equity within minoritized communities, to advance health literacy on AMR, and to establish easily accessible opportunities for vaccination. Finally, we must advocate for funding to be specifically allocated to institutions that primarily serve minoritized groups so they have access to novel medications and diagnostics tools and can employ the necessary personnel to effectively reduce AMR. Overall, a proactive approach is necessary to address the factors that contribute to AMR racial inequities.


Cancer is one of the leading cause of morbidity and mortality worldwide. The development of chemotherapeutic drug resistance, which causes the disease to reoccur, has decreased the effectiveness of cancer treatments. Proteolysis-targeting chimaera (PROTACs) are protein targeting chimeric molecules that have the capacity to bind disease-causing protein of interest with a high degree of specificity and then lyse it. PROTACs are specialized, adaptable, and biologically active. They have tremendous advantages over other types of inhibitors which are not able to give protection against the drug resistivity Research Topic in cancer as they have the ability to trigger selective intracellular proteolysis, which can be utilized to specifically target and destroy tumor-promoting proteins inside of cells. To enhance their therapeutic outcomes, new understandings of the molecular mechanisms of PROTAC-mediated degradation are required.• Molecular underpinnings of PROTAC-mediated protein degradation• Modulation of the ubiquitination system for cancer treatment• Innovative designing and development of PROTACS-based therapeutics• Comparison of PROTACs with non-targeted and targeted therapiesThe current Research Topic aims to explore the most recent developments in the creation and use of PROTACS-based treatments for cancer. We invite research articles, review articles, and viewpoints that address to the following Research Topic, but are not restricted to them.This Research Topic brings together several scientific contributions that highlight some extremely exciting findings. The published articles on this Research Topic have attracted significant interest from both academia and industry.Zheng et al. submitted a comprehensive review on this subject in order to address cancer drug resistance, which is a significant obstacle to the successful treatment of malignancies going forward. Recent developments in this field of study show that PROTACs can successfully destroy targets that confer cancer resistance to therapies, building the foundation for next-generation therapies and that provide additional clinical benefit to patients.Juan et al. have proposed methods to enhance their therapeutic efficacy and the development of fine-tuned nanoparticles based delivery systems to increase the bioactivity of PROTACs.The authors provided an overview of the current use of PROTACs to treat solid tumors and included recommendations for overcoming their clinical development roadblocks. Among designing and development constraints, improvements in bioavailability and safety brought about by an improved delivery route seem to be relevant. In light of this, Luo et al.). The emphasis of the authors has been on the molecular design of PROTACs using various methodologies, which provides a deeper mechanistic knowledge of developing degraders and serves as a beneficial roadmap for the advancement of the upcoming degrader technologies. Anwar et al. published a very thorough analysis of PROTACs designed to combat different forms of leukaemia and blood cancers. Along with all of this material, another investigation focused on how YAP1 deacetylation promoted chemotherapy resistance and targeted treatment in FLT3-ITD+ AML cells . This research demonstrates that the FLT3-ITD+ AML cells are maintained by the HDAC10-YAP1-PARP1 axis, and blocking this axis may improve the clinical outcomes for FLT3-ITD+ AML patients.Significant developments in newly developed degrader technologies were also reported in this area (We anticipate that this Research Topic will offer an informative guide to understanding this cutting-edge technology which can be employed as tools for targeted therapies and drug development.


Electrospinning is the simplest and most widely used technology for producing ultra-thin fibers. During electrospinning, the high voltage causes a thin jet to be launched from the liquid polymer and then deposited onto the grounded collector. Depending on the type of the fluid, solution and melt electrospinning are distinguished. The morphology and physicochemical properties of the produced fibers depend on many factors, which can be categorized into three groups: process parameters, material properties, and ambient parameters. In the biomedical field, electrospun nanofibers have a wide variety of applications ranging from medication delivery systems to tissue engineering scaffolds and soft electronics. Many of these showed promising results for potential use as medical devices in the future. Medical devices are used to cure, prevent, or diagnose diseases without the presence of any active pharmaceutical ingredients. The regulation of conventional medical devices is strict and carefully controlled; however, it is not yet properly defined in the case of nanotechnology-made devices. This review is divided into two parts. The first part provides an overview on electrospinning through several examples, while the second part focuses on developments in the field of electrospun medical devices. Additionally, the relevant regulatory framework is summarized at the end of this paper. Nanofibers are unidirectionally elongated polymer-based solid structures with a nanosized diameter. The fabrication of nanofibers is possible in numerous ways, e.g., self-assembly, melt blowing, and drawing, although electrospinning is the most common. Electrospun nanofibers have various applications under investigation, such as functional textiles, functional clothing, skincare and cosmetics, electronics, acoustics, composites, filters, and biomedical uses . The latChronic or non-healing wounds develop when any acute wound fails to heal in the expected time frame for that type of wound, which might be a couple of weeks or up to six weeks. Ulcers are the most common type of chronic wound, which may be caused by constant pressure (decubitus ulcer), venous or arterial circulatory problems, or diabetic angio-neuropathy. These wounds need special care and innovative dressings to promote the healing process . The wouTissue engineering involves the implantation of a natural, semi-synthetic, or synthetic implant to repair damaged tissue. The closer the implant’s properties are to the original tissue, the more successful the operation. As a result, while autograft is the best option in this case, it is not always feasible. Scaffolds primarily comprised of polymeric biomaterials provide structural support for cell adhesion and subsequent tissue formation when synthetic or semi-synthetic implants are required. One suitable way to create differently designed scaffolds is electrospinning .®  95/99.The COVID-19 pandemic spotlighted the importance of personal protective equipment, such as face masks. Face masks proved to reduce the human-to-human transmission of the virus by stopping the spread of virus-containing saliva and respiratory droplets . TypicalThe regulation of substances and devices used to maintain and restore health is receiving particular attention worldwide. The two bodies that have a significant influence on other countries’ national agencies are the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA); however, the World Health Organization (WHO) also regularly gives guidelines and publishes various tools for national health systems. Generally, the regulation of conventional medical devices is well-defined, although it is not harmonized between countries . HoweverThe healthcare industry is regulated by strict rules, so considering regulatory requirements at the development stage can be worthwhile. To the best of the authors’ knowledge, there is no published review of the regulatory aspects of nanofibers developed as potential medical devices in the literature. In the first part of this review, the basic principles of electrospinning, the effects of the different parameters on the process and the produced fibers, and the types of solvent and melt electrospinning techniques are discussed. In the second part, the focus is on electrospun medical devices. After a summary of the possible areas of application, their regulatory approach is described.The most common production method for nanofibers is electrospinning due to its simplicity and industrial scalability. Electrospinning is an electrohydrodynamic phenomenon in which the fibers are formed by drawing out a polymer jet under a high electric field. To accomplish this, a fluid polymer is required at the starting point, which can be either a polymer solution/emulsion or a melted polymer. Accordingly, solution, emulsion, and melt electrospinning methods can be distinguished. The methods are described in greater depth later.−7–10−3 mA) [Generally, electrospinning is driven by the electrostatic potential characterized by high voltage (some tens of kV) and very low current (1010−3 mA) . The mosIn all cases, the initial step in electrospinning is the formation of the Taylor cone. The surface tension always attempts to reduce the surface area of a liquid, the polymer droplet tends to be spherical in the absence of a strong voltage A. HoweveProcess parameters ;Material properties ;Ambient parameters (temperature and humidity).The factors that determine the properties of nanofibers are usually grouped into three categories :Process Among the process parameters, the applied high voltage has the greatest influence on the mechanism of electrospinning and thus the morphology of the formed fibers. Generally, a higher applied voltage stretches the polymer liquid more, resulting in thinner fibers ,13. HoweIn addition to the high voltage, other factors may influence the electrospinning process. Certainly, it can be influenced by the equipment itself and the process parameters. The equipment can have three different orientations depending on the initial and target positions of the jet. The electrospinning setup can be horizontal or, in the case of a vertical arrangement, top-down or bottom-up. The degree to which the electrical force and gravitational force contribute differs among the different setups. Although this is often overlooked, the gravitational force could influence the shape of the Taylor cone, jet trajectory, fiber diameter, distribution, and overall spinning efficiency according to Suresh et al. .Additionally, to obtain uniform nanofibers on the collector, complete drying of the jet, meaning evaporation of the solvent or solidification of the melted polymer, is required. Therefore, the jet requires an appropriate flight time in the air while whipping toward the collector. With a longer distance, the flight time increases, and thinner fibers will be formed. In this way, the flight distance of the jet (tip-to-collector distance in the case of nozzle electrospinning) affects the fiber morphology ,18. HoweDuring production, the electrospun nanofibers are deposited on the collector, forming the nanofiber mat on its surface. The orientation of the fibers is affected by the type of collector. The random fiber orientation is sufficient for the majority of drug delivery applications. Nevertheless, some fields (mainly tissue engineering) require structured scaffolds with aligned fibers . The basIn nozzle-based electrospinning, the liquid polymer is fed continuously from a syringe through a nozzle into the electric field by a pump. The process is influenced by the feeding rate. If the feeding rate is increased while the voltage remains constant, the diameter of the collected fibers will increase ,25. Too Among the material properties, the type of polymer affects the charge of the electrospinning liquid. According to the paper of Tong et al., electrospinning of cationic polymers  is only achievable with a positively charged spinneret . The numAngammana et al. investigated different poly(ethylene oxide) (PEO) nanofibers by varying conductivity in electrospinning solutions by dissolving sodium chloride. By increasing conductivity, the results showed three phases. In the first phase (0–200 μs/mm), the average jet current increased and the average fiber diameter decreased. However, in the second phase (200–2000 μs/mm), the average jet current slightly decreased, while the fiber diameter kept decreasing. A further increase in conductivity resulted in intermittent or no jet .The polymer’s molecular weight should also be taken into account. In general, a higher molecular weight is preferable because longer polymer chains facilitate the formation of nanofibers by entangling better . FurtherThe effect of surface tension was also studied in the same article by Feng et al. In their case, it was necessary to reduce the surface tension with the use of ethanol to form beadless fibers of chitosan . In geneIn the case of solvent electrospinning, the type of solvent also influences the structure and properties of the nanofibers formed. Song et al. investigated the effects of different deionized water–ethanol solvent mixtures as solvents of PEO. The results revealed that the type and volatility of the solvent mixture determine many properties of the nanofibers. In brief, with the increase in ethanol, the average fiber diameter significantly increased, the diameter distribution widened, the surface of the nanofibers became rough, and the productivity decreased. Furthermore, as the ethanol content increased, the molecular chain orientation and crystallinity degree decreased .Aside from material attributes and process parameters, ambient parameters such as temperature and relative humidity also affect the electrospinning process and the properties of the obtained nanofibers. The solvent appears to evaporate faster in a warmer environment. Moreover, the environmental temperature affects such properties of the polymer solution or melt as viscosity, surface tension, and conductivity as well . Vrieze Relative humidity can have a significant impact on the electrospinning process . At veryOn the contrary, in the case of hydrophobic polymers, greater humidity leads to the formation of porous nanofibers as a consequence of the complex interaction between water as a non-solvent, the hygroscopic solvent of the polymer, and the polymer itself ,39.As already mentioned above, solution, emulsion, and melt electrospinning can be distinguished. The three methods follow the same main principles, although there are notable differences. Solution and emulsion electrospinning processes are very similar regarding their equipment, advantages, and limitations. The main difference is the type of polymer liquid, as their names imply.On the other hand, for melt electrospinning, heating is required to melt the polymer. For this reason, an additional heating component is needed, which causes a more complex electrospinning setup. Additionally, both the nanofiber-forming polymer and the active ingredient must be thermally stable, which limits the choice of materials. However, some polymers  cannot be dissolved, only melted before spinning. Moreover, the absence of solvent makes the melt method environmentally friendly. Finally, melt electrospinning is comparable to additive manufacturing techniques and thus can be utilized to create special three-dimensional electrospun nanofiber scaffolds for regenerative medicine applications .As mentioned above, solution and melt electrospinning are the two major types of the electrospun nanofiber production process. Despite the fact that more articles on the topic are published each year, the vast majority of them are about solution electrospinning. According to Calori et al., approximately 90% of the ultrafine-based scaffolds were produced by solvent electrospinning in 2020 . The popGenerally, the basic solution electrospinning setup contains a high-voltage supply and a polymer container, practically a syringe, a pump, a spinneret (needle or nozzle), and a collector. A single-needle or single-nozzle configuration is the simplest and most common, where the Taylor cone is created on the top of the capillary. It can provide uniform nanofibers from a single-polymer solution or polymer blend . Even ifNormally, a single Taylor cone appears at the tip of the spinneret, from which a single jet is ejected. Hence, scaling up the process requires several spinnerets connected in parallel. This so-called multi-nozzle electrospinning method combines the benefits of nozzle-based electrospinning in addition to the ability to produce nanofibers in industrially relevant volumes. Nonetheless, the method is challenging because the presence of several jets at the same time modifies the electric field and the charged jets interact with each other, which increases the difficulty in collecting nanofibers . In thisThe main drawback of single-nozzle electrospinning is the limited production capacity (0.01–0.1 g/h) . This crNozzle-free electrospinning can be divided into two groups depending on whether the set-up is equipped with a stationary or a rotating spinneret . Simple During emulsion electrospinning, the homogenous mixtures of two or more immiscible liquids are electrospun. The method is very similar to single-needle solution electrospinning; however, the obtained nanofibers have a core–shell structure . The advThe other large group of electrospinning methods is melt electrospinning, in which the charged jet is drawn out of a polymer melt. The active ingredient and/or excipients can be dissolved in the molten polymer if not only the pure polymer nanofiber is desired. As there is no solvent to evaporate in melt electrospinning, only heat transfer occurs during the travel of the jet. The absence of residual solvent is desirable for some biological applications . HencefoThe setup for melt electrospinning generally consists of a high-voltage power supply, a polymer container, a heating device, a spinneret, and a collector. The type of melt electrospinning depends on whether the polymer container is a syringe or something else .A plastic or glass syringe reservoir and a metal needle spinneret are major parts of melt electrospinning systems. The main advantages of this setup are the standardized holding capacity and nozzle sizes, the standard polymer delivery, and the interchangeability . The syrZhou et al. pointed out that the temperatures at the spinneret and in the spinning region are critical to producing sub-micron-sized fibers. If the environmental temperature was below the glass transition temperature of the polymer, the too fast solidification of the jet led to an increased fiber diameter .The two main disadvantages of syringe-based melt electrospinning are the potential degradation of the polymer or active ingredient at high temperatures and the larger fiber diameter with less controllable morphology compared with solvent electrospinning . To over2 laser. Rapid and uniform laser heating can minimize polymer degradation and facilitate the production of tissue engineering nanofiber scaffolds [Li et al. reported promising results using laser melt electrospinning, a technique that is similar to commercial fused deposition modeling (FDM). In this setup, a solid polymer rod is fed into the heating zone of the COcaffolds .There are various articles about reducing fiber diameter, some of which are provided here. Malakhov et al. used a screw extruder instead of a syringe to deliver a constant supply of polymer to the spinneret . MorikawElectrospun nanofibers have a broad range of potential biomedical applications, including drug delivery systems, wound dressings, tissue engineering scaffolds, various diagnostic tools, in vivo models, and filters, which can be produced via electrospinning. As drug delivery systems, nanofibers can increase the solubility and permeability of BSC II/IV active pharmaceutical ingredients, improve the therapeutic effect, reduce the side effects and toxicity, and facilitate alternative administration. Additional benefits are the tailorable release profile, the high loading capacity, the high encapsulation efficiency, the ease of operation, and the cost-effectiveness .As in wound dressings and tissue engineering, the ability of nanofibers to produce aligned scaffolds capable of mimicking the extracellular matrix is exploited ,75. The Nanofibers offer the benefits of flexibility and/or stretchability, conductivity, and transparency, as well as a large surface area and diverse fiber morphology for biosensors and other soft electronics . It is aIndeed, it is useful to distinguish between pharmaceuticals and medical devices when considering the use of nanofibers in biomedicine. The two categories are similar in that both are used to cure, prevent, or diagnose diseases. The difference is that pharmaceuticals contain active substances, which are chemicals in nature and actively interact with the human body. Thus, drug-loaded nanofibers belong to this category. In contrast, medical devices do not contain any active substance, so they do not achieve their purpose through chemical action. The exact definition of medical devices by the WHO is: “An article, instrument, apparatus or machine that is used in the prevention, diagnosis or treatment of illness or disease, or for detecting, measuring, restoring, correcting or modifying the structure or function of the body for some health purpose. Typically, the purpose of a medical device is not achieved by pharmacological, immunological or metabolic means” . AccordiIn addition, medical equipment is a large, special group within medical devices. The WHO definition is the following: “Medical devices requiring calibration, maintenance, repair, user training, and decommissioning—activities usually managed by clinical engineers. Medical equipment is used for the specific purposes of diagnosis and treatment of disease or rehabilitation following disease or injury; it can be used either alone or in combination with any accessory, consumable, or other piece of medical equipment. Medical equipment excludes implantable, disposable, or single-use medical devices”. Electrospun nanofibers provide a wealth of opportunities in the area of soft electronics, such as electrodes, conductors, different kinds of sensors, and batteries. Wang et al. recently released a comprehensive review of this field . This arThe COVID-19 pandemic has recently led to an increased need for face masks, which has boosted research as well. Because the face mask serves as a barrier, the vast surface area and small pore size of electrospun nanofiber mats are preferable. Leung and Sun charged the produced nanofiber filter after electrospinning due to the hypothesis that the negatively charged coronavirus adheres more strongly to positively charged nanofibers. Even at an ultralow pressure drop, the produced filters attained 90% efficiency .For chronic wound management, nanofiber dressings have great potential as they provide most of the properties of the ideal dressing, such as protection against bacteria and external aggression, absorption of excess exudates, adequate gas exchange, providing a moist environment, being painless for the patient, and easily removable. Moreover, electrospun nanofibers can mimic the extracellular matrix; regulate skin cell responses, including proliferation, migration, and differentiation; and thus reduce wound healing time radically; therefore, chronic wounds that are not-healing  can be closed. Wound healing nanofibers are the subject of extensive research, and the results have been provided in various review publications ,137,138.The scientific debate over tissue engineering nanofibers is also heated. In general, nanofiber scaffolds have several beneficial properties to provide adequate tissue replacement, such as high porosity, large surface area, biodegradability, biocompatibility, and tailorable 3D architecture. They can provide excellent support for cell adhesion, proliferation, and differentiation due to their ability to mimic the required extracellular matrix in biological and mechanical features, such as alignment, nano-topography, stiffness, and tensile strength. By choosing the right method and collector, similar structures to the original tissue can be achieved. With the use of co-electrospinning, coaxial electrospinning, or other switched techniques, the structure possibilities are even wider. Wakuda et al. used coaxial electrospinning to produce non-water-soluble collagen hydrogel nanofibers without using any cross-linkers. The electrospinning resulted in collagen core and PVP shell fibers, which were immersed in ethanol to wash away the PVP shell and gel the collagen. They obtained promising results using human umbilical vein endothelial cells as a potential vascular scaffold . Wang etIn addition to developing new implantable scaffolds, electrospinning is a suitable technique to innovate existing medical devices, e.g., to coat vascular stents or orthopedic implants. The aim could be to prevent neointimal hyperplasia through the local delivery of selective pleiotropic drugs .As previously stated in paragraph 5, pharmaceuticals and medical devices are distinguished by the presence or absence of pharmacological effects on the human body. According to the Global Harmonization Task Force’s definition, which is used by the WHO, a medical device, “does not achieve its primary intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its intended function by such means” . HoweverAll medical devices in the USA are regulated by the FDA under the Center for Devices and Radiological Health (CDRH). It differentiates three regulatory classes based on the level of control required to assure the safety and efficacy of the device . Class IThe regulatory process for medical devices in the EU is at the member-state level; however, the EMA is also involved. For example, drug-eluting stents belong to the group “medical devices with an ancillary medicinal substance”, so the EMA plays a role in their assessment—they must meet the requirements of the medical device legislation and be CE marked . The manThe classification of medical devices in the EU is according to the Regulation (EU) 2017/745 and contains four levels: Class I, Class IIa, Class IIb, and Class III . The risFurthermore, Special Rule 19 applies to all nanomaterial-associated devices; however, they belong to Class IIa, IIb, or III according to the potential for internal exposure . If the Clinical investigation of a medical device can be any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device. It is regulated by the ISO 14155:2020  standard . In geneElectrospun nanofibers are nanomaterials because of their nano-sized diameter. At present, the regulation of nanomedicine is not clear, and the number of specific regulatory guidance documents is poor. Different definitions of nanomaterials have been made by different bodies, such as the US National Institute of Health, the European Science Foundation, and the European Technology Platform. Despite that, over 50 nanomedicines (mainly anti-cancer medicines) have been approved and are currently available on the market . RecentlFree nanomaterials added to a medical device ;Fixed nanomaterials form a coating on implants to increase biocompatibility  or to prevent infection ;Embedded nanomaterials to strengthen biomaterials  .Specifically related to medical devices, the European Commission published the “Guidance on the Determination of Potential Health Effects of Nanomaterials Used in Medical Devices” in 2015. The guidance draws attention to the use of the ISO 10993-1  standard. Moreover, this guidance describes examples that could be produced by electrospinning, namely:Face masks have recently received increased attention due to the COVID-19 pandemic. In March 2020, the FDA issued emergency use authorizations for personal respiratory protective devices . There aConcerning nanofibrous medical devices, some early birds are on the market or in the pipeline .®, an FDA-approved common dural sealant [When developing nanofibers as a potential medical device, there are a few things that should be considered in the early stages of research that could be important from a regulatory perspective. First, the materials used must satisfy the safety requirements. It is recommended to choose a polymer that is considered safe and has been approved by the authorities. Biocompatible and biodegradable polymers are generally preferred. A good strategy could be the innovation of an already authorized device by electrospinning. Campbell et al. made nanofibers from an FDA-approved cyanoacrylate polymer for closing endonasal surgical defects and compared them with Adherus sealant . Second, sealant . Moreove sealant .Electrospinning is the easiest and most common method for nanofiber fabrication. The number of polymers that can be used is extensive; however, the material properties have a significant impact on the fibers produced, e.g., the viscosity of the liquid polymer is crucial. Additionally, process and ambient parameters affect the electrospinning process and the properties of the fibers. Voltage is considered to be the most influential factor; however, it should be pointed out that the type of collector determines the arrangement of the fibers within the mat.Electrospun nanofibers have unique physical characteristics that make them suitable for the development of various medical devices, such as dressings for chronic wounds, tissue engineering scaffolds, filters, and soft electronics. Each of these requires different morphologies, physicochemical properties, and architectures of nanofiber mats, all of which can be achieved using various electrospinning techniques. The two major types are solution and melt electrospinning. The previous can be subdivided according to the presence and type of the nozzle. Various nozzle-free techniques have been developed to increase productivity and prevent needle clogging; however, they have not overtaken the popularity of nozzle-based techniques. Side-by-side and coaxial nozzles can provide the controlled location of different polymers within the fiber, creating Janus and core–shell nanofibers, respectively. Melt electrospinning can be subdivided into syringe-based and syringe-free methods and has two main advantages. First of all, it is considered a green technique due to the absence of solvent, which is beneficial in the production of medical devices. Secondly, melt electrospinning drawing enables the building of mats with more complex structures, which can be applied to the fabrication of tissue regeneration scaffolds.The potential biomedical applications of electrospun nanofibers differ from drug delivery systems to various medical devices, such as filters, soft electronics, tissue engineering scaffolds, and wound dressings. Generally, the large surface area, the tailorable morphology, and the large range of polymers that can be used are the common advantages. Moreover, nanofibers have additional benefits in every field of application, for example, small pore size and flexibility as face masks or biocompatibility and similarity to the extracellular matrix as wound care and implantable devices. In the field of tissue engineering, the most investigated tissues and organs are the bones, the blood vessels, the skin, and other soft tissues , but the research is also intensive on cardiac, neural, and cartilage replacements. The challenges and future direction of electrospinning-based biomedical scaffolds are the development of the capability for reproducible, industrial-scale production and extensive pre-clinical and clinical testing before commercialization .In the case of nanofibrous medical devices, basic research is very intensive, but only a few products have received marketing approval so far. Despite the well-defined regulatory approach of medical devices in general, the regulation of nanomaterial-containing ones is unclear. It is agreed that caution is necessary and that nanomaterial-containing medical devices should be classified into higher-risk categories. The guidelines published by the EU and the relevant ISO standards are certainly good cornerstones, and on specific issues, consultation with the authorities might also help. After classification, the rules applicable to the class must be followed.