The number of Wyckoff sequences of a given subdivision complexity is calculated by means of a generating polynomial approach and a dynamic programming approach. The result depends on the choice of space-group symmetry (which is obligatory) and Wyckoff sequence length . It also takes into account specified values for the total number of combinatorial and coordinational degrees of freedom, thereby representing crystal structures of invariant subdivision complexity. Wyckoff sequences are a way of encoding combinatorial information about crystal structures of a given symmetry. In particular, they offer an easy access to the calculation of a crystal structure’s combinatorial, coordinational and configurational complexity, taking into account the individual multiplicities  and arities  associated with each Wyckoff position. However, distinct Wyckoff sequences can yield the same total numbers of combinatorial and coordinational degrees of freedom. In this case, they share the same value for their Shannon entropy based subdivision complexity. The enumeration of Wyckoff sequences with this property is a combinatorial problem solved in this work, first in the general case of fixed subdivision complexity but non-specified Wyckoff sequence length, and second for the restricted case of Wyckoff sequences of both fixed subdivision complexity and fixed Wyckoff sequence length. The combinatorial results are accompanied by calculations of the combinatorial, coordinational, configurational and subdivision complexities, performed on Wyckoff sequences representing actual crystal structures. Since the Wyckoff sequence composed of these letters does not include any specific information about either the unit-cell parameters or the atomic coordinates, it is a more abstract notion as well, and useful as such for purposes of crystal structure classification and systematics  and, if present, special position(s) of their corresponding space-group type. Indeed, the Wyckoff sequence has been used in the aforementioned sense, as a coordinate-free representation of crystal structures in modern machine learning approaches to materials discovery  with ν = 19 non-fixed sites and φ = 8 fixed ones, constituting the case with the highest number of possible sequences, this would correspond to about k = 50 inclusive  and coordinational (A) collective degrees of freedom, associated with a weighted sum of each Wyckoff position’s individual multiplicity  and coordinational (A) degrees of freedom. In a similar way, on the Wyckoff position level, the collective combinatorial and coordinational degrees of freedom, M or A, result as the sum of the individual combinatorial and coordinational degrees of freedom, Taking a general point of view, the collective degrees of freedom represent a certain system (a macrostate), while the individual degrees of freedom each represent a certain subsystem (a microstate). This is true on different levels of hierarchy. For instance, on the crystal structure level, the collective configurational degrees of freedom, i.e. modulo centring translations, which, in the following, will be the preferred choice of description), while the possible values of the Wyckoff arities are restricted to the set In combinatorial terms this splitting of a system into subsystems corresponds to an integer partition. However, in their crystallographic application, the number of partitions is not simply given by the number-theoretic partition function, yet restricted by crystallographic symmetry and the coupling of combinatorial and coordinational degrees of freedoms as found within each Wyckoff position. In particular, the possible values of the Wyckoff multiplicities considering all space-group types are restricted to the set Thus, due to these particular restrictions, it is a non-trivial task to describe a macrostate defined by the collective degrees of freedom The following section will give the answer to this question, with the main results being a generating polynomial approach (Section 2.42.k) exist, given a pair of combinatorial and coordinational degrees of freedom To state the problem succinctly: how many distinct Wyckoff sequences  using the routine WYCKPOS , if the primitive unit cell, and the number of atoms it contains, is taken as a reference. Indeed, choosing the primitive unit cell as a reference is strongly recommended in the context of crystallographic complexity calculations em Fig. 1, in whici is the imaginary unit  matching the number of distinct types of coins with the number of distinct Wyckoff positions; (ii) identifying the values of distinct types of coins with the Thus, in some way, the crystallographic problem is a coin change problem with a twist, based on imaginary coins with denominations on both their front and back sides and a pair of target values to reach upon summation. Similar combinatorial problems arise for the case of real cards, coupling values denoted by digits or letters with symbolic ones such as diamonds, hearts, spades and clubs.n Wyckoff positions, In particular, the third adaptation step is crucial for the correct enumeration. As a consequence of it, generating polynomials of the kind n sites can be split, As an aside, one can note that the product over all z into the respective polynomials with all other procedures considered to be analogously performed. However, there is a difference, in that the atomic numbers are not restricted in any way, that is to say there exists no natural coupling between them and the Wyckoff multiplicities and arities – they are a pure matter of choice. In contrast, the Wyckoff multiplicities and arities are coupled in their values for each Wyckoff position of a space group. Thus, regarding this relative arbitrariness of choice and the relative unimportance of this general case, we refrain from expanding in this direction for the moment. However, our opinion on this topic might change in the future, if there should be an interesting application for fixing the total chemical degrees of freedom, that is the total electron count within a reduced unit cell, to a set value, together with the other degrees of freedom, and asking for the number of crystal structures fulfilling this condition. In this case, any generalization required can be obtained in a straightforward manner by following the same extension procedure as described in the following.It should be noted that this approach can be further generalized, in principle, by taking into account chemical degrees of freedom [as introduced by Hornfeck 2020] in term2.5.k of the Wyckoff sequence as a further restriction, which can be seen as an extension and a refinement to a previous result in the combinatorics of Wyckoff sequences , and how the polynomials corresponding to the non-fixed sites are restricted in terms of the monomials of highest degree in either x or y by the given values of either M or A or both.Now, with some arbitrary chosen n sites into ν contributions from the non-fixed sites (bivariate case) and φ contributions from the fixed ones (univariate case)  and 2CoAl7Ge4/LiSmTiO4 prototypes).Of these, 55 correspond to a unique pair On the basis of this work, one obtains a larger number of 44 possible Wyckoff letter sequence solutions [based on the Wyckoff multiplicities and arities, compare equation (21)4.2.F-centred unit cell would be four times larger. Again, all of the four possible values for the Wyckoff arity are present in this example, in addition to seven distinct values for the Wyckoff multiplicity. This example was chosen because it partly corresponds to actual crystal structures.As another example, we consider the cubic space-group type Now, for the given choice of If one performs the same calculation with the additional restriction of the Wyckoff sequence length to the value 4.3.Cmcm (No. 63) encompassing a total of eight distinct Wyckoff positions of the following multiplicities and arities: C-centred unit cell would be two times larger. Again, all of the four possible values for the Wyckoff arity are present in this example, in addition to three distinct values for the Wyckoff multiplicity.As a final example, we consider the orthorhombic space-group type Now, for the given choice of 5.As a contribution to the combinatorics of Wyckoff sequences, we have presented two methods to calculate their number for a fixed space group, given a pair of combinatorial and coordinational total degrees of freedom, and, optionally, their length. The first method is based on a generating polynomial approach (see Sections 2.4


The optimal timing of endoscopy in liver cirrhosis with acute variceal bleeding (AVB) remains controversial in current guidelines and studies.Consecutive patients with liver cirrhosis and AVB were screened. The timing of endoscopy was calculated from the last presentation of AVB or the admission to endoscopy. Early endoscopy was defined as the interval < 12 h, < 24 h, or < 48 h. A 1:1 propensity score matching (PSM) analysis was performed. Five-day failure to control bleeding and in-hospital mortality were evaluated.Overall, 534 patients were included. When the timing of endoscopy was calculated from the last presentation of AVB, PSM analysis demonstrated that the rate of 5-day failure to control bleeding was significantly higher in early endoscopy group defined as < 48 h , but not < 12 h  or < 24 h , and that the in-hospital mortality was not significantly different between early and delayed endoscopy groups . When the timing of endoscopy was calculated from the admission, PSM analyses did not demonstrate any significant difference in the rate of 5-day failure to control bleeding  or in-hospital mortality  between early and delayed endoscopy groups.Our study could not support any significant association of timing of endoscopy with cirrhotic patients with AVB.The online version contains supplementary material available at 10.1186/s12876-023-02766-8. Acute variceal bleeding (AVB) is a fatal complication in liver cirrhosis. The incidence of variceal bleeding is about 10-15% per year and 6-week mortality is 10–20% . CurrentDespite endoscopy is the mainstay choice of treatment for AVB in patients with cirrhosis, the timing of endoscopy remains controversial in current guidelines. The Baveno VI consensus, the American Association for the Study of Liver Diseases (AASLD) practice guideline, the Belgian guideline, and the European Society of Gastrointestinal Endoscopy (ESGE) guideline recommend endoscopy within 12 h of presentation of AVB , 5, 6. TPrevious studies regarding the timing of endoscopy in liver cirrhosis with AVB had contradictory conclusions. A retrospective cohort study, including 311 patients with cirrhosis and AVB, found that delayed endoscopy (> 15 h) was an independent risk factor for in-hospital mortality . HoweverMore recently, a large randomized controlled trial (RCT) did not demonstrate any significant difference in 30-day mortality between patients with upper gastrointestinal bleeding treated with urgent endoscopy (< 6 h) and early endoscopy (6-24 h) . HoweverHerein, we conducted a retrospective study to further shed light on whether early endoscopy was beneficial for patients with cirrhosis and AVB, especially by adjusting for the definitions regarding timing of endoscopy and early endoscopy, manifestation of AVB, and severity of liver disease.Patients with liver cirrhosis and AVB were screened from our retrospective database of 982 patients with liver cirrhosis and acute upper gastrointestinal bleeding (AUGIB) who were consecutively admitted to our hospital between January 2010 and June 2014 , 14 and Exclusion criteria were as follows: (1) patients did not undergo endoscopy or those with contraindications for endoscopy; (2) patients underwent endoscopy at other hospitals or emergency department or outpatient clinics of our hospital; (3) endoscopy was performed beyond 5 days after the last episode of AUGIB; (4) the timing of endoscopy was ambiguous according to the medical records; and (5) the source of AUGIB was non-variceal or could not be accurately identified according to the medical records or endoscopic reports.The study protocol has been approved by the Medical Ethical Committee of the General Hospital of Northern Theater Command with an approval number (Y [2022] 019) and performed according to the Declaration of Helsinki. Written informed consents were waived due to the retrospective nature of this study.Primary data extracted included age, gender, clinical manifestations, etiology of liver disease, presence of hepatocellular carcinoma, systolic blood pressure, heart rate, hemoglobin, white blood cell, platelet count, albumin, alanine aminotransferase, blood urea nitrogen, serum creatinine, sodium, and prothrombin time (PT) at admission. Active variceal bleeding on endoscopy, source of variceal bleeding, endoscopic variceal therapy, surgery or interventional treatment, Child-Pugh score and class, and model for end-stage liver disease (MELD) score were also recorded.Outcomes of interest included 5-day failure to control bleeding and in-hospital death.Timing of endoscopy was calculated according to the interval from the last presentation of AUGIB or the admission to endoscopy. Accordingly, eligible patients were divided into early and delayed endoscopy groups according to three different intervals, including < 12 h versus ≥ 12 h, < 24 h versus ≥ 24 h, and < 48 h versus ≥ 48 h.AUGIB was defined as hematemesis or melena within 120 h before admission . Five-daGenerally, the management of AUGIB is in accordance with the current practice guideline, which primarily includes fluid resuscitation, blood transfusion, pharmacological treatment, and endoscopic treatment , 8. Red Continuous variables were presented as mean ± standard deviation and median (range), and categorical variables were presented as frequency (percentage). The non-parametric Mann-Whitney U test was used for continuous variables, and the chi-square test and Fisher’s exact test were used for categorical variables to explore the difference between early and delayed endoscopy groups. Logistic and Cox regression analyses were performed to identify whether early endoscopy was an independent predictor of 5-day failure to control bleeding or in-hospital death. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. A 1:1 propensity score matching (PSM) analysis was performed by using a matching tolerance of 0.02 and greedy-matching algorithm without replacement to compare the rate of 5-day failure to control bleeding and in-hospital mortality between early and delayed endoscopy groups. After PSM, the comparability of baseline characteristics between the groups was re-evaluated. Matching factors included age, gender, systolic blood pressure < 90mmHg, heart rate > 100 beats per minute, PT, Child-Pugh score, MELD score, hematemesis at admission, active variceal bleeding on endoscopy, and endoscopic variceal therapy. A two-tailed P < 0.05 was considered statistically significant. All statistical analyses were performed with IBM SPSS 26.0 .Overall, 534 patients with cirrhosis and AVB were included Fig. . Patient< 12 h versus ≥ 12 h. In the overall-analysis, early endoscopy group had significantly higher proportions of hepatitis C virus (HCV) infection and systolic blood pressure < 90 mmHg and white blood cell than delayed endoscopy group . Multivariate Cox regression analysis showed that the interval from last presentation of AVB to endoscopy < 12 h was not significantly associated with in-hospital death .In the PSM analysis, 46 patients were matched to each group . Multivariate Cox regression analysis showed that the interval from last presentation of AVB to endoscopy < 24 h was not significantly associated with in-hospital death .In the PSM analysis, 97 patients were matched to each group . Cox regression analysis showed that the interval from last presentation of AVB to endoscopy < 48 h was not significantly associated with in-hospital death .In the PSM analysis, 165 patients were matched to each group . Multivariate Cox regression analysis showed that the interval from admission to endoscopy < 12 h was not significantly associated with in-hospital death .In the PSM analysis, 63 patients were matched to each group . Multivariate Cox regression analysis showed that the interval from admission to endoscopy < 24 h was not significantly associated with in-hospital death .In the PSM analysis, 155 patients were matched to each group . Multivariate Cox regression analysis showed that the interval from admission to endoscopy < 48 h was not significantly associated with in-hospital death .In the PSM analysis, 199 patients were matched to each group  and severity of liver diseases (Child-Pugh class A versus Child-Pugh class B/C). The results were shown in Supplementary Table Based on the data obtained from our center, the benefit of early endoscopy on the outcomes of patients with liver cirrhosis and AVB could not be supported. It seems to be contrary to the traditional concept that early endoscopy could achieve more rapid hemostasis and hence better outcomes. Notably, early endoscopy may influence basic resuscitation, leading to ischemic complications, and shorten the duration of action of vasoactive drugs or antibiotics before endoscopic treatment for acute gastrointestinal bleeding . AdditioOur finding may be influenced by the definition regarding time to endoscopy, the manifestation of AVB, or the severity of liver dysfunction. First, until now, any standard definition regarding time to endoscopy has not been given by any practice guideline yet , 19, 20.Second, patients with cirrhosis and AVB who presented with hematemesis at admission may have worse prognosis than those who presented with melena . The resThird, the severity of liver cirrhosis affects the prognosis of AVB . It has Our study has several limitations as follows. First, our study was retrospective. The selection of emergency endoscopy often depends on the patients’ conditions, physicians’ decisions, and availability of endoscopists, which leads to a considerable selection bias. Specifically, patients with massive hematemesis who were not effectively treated by drugs were more prone to early endoscopy, those with hemodynamic instability would undergo delayed endoscopy after basic resuscitation, and those admitted during off-hours might undergo delayed endoscopy. Although all procedures were performed by experienced endoscopists, it may be different in judging the source of gastrointestinal bleeding and treating AVB under endoscopy among endoscopists, which influences the prognosis of patients. In addition, endoscopic findings in the stomach were retrospectively derived from the patients’ medical records alone, but they seemed to be insufficient to evaluate whether gastric contents had influenced the efficacy of gastric variceal treatment under endoscopy. Second, our study excluded patients who had undergone endoscopy at their local hospitals and outpatient and emergency departments, those who were not suitable for endoscopy, as well as those who died before endoscopy. Such patients should be more severe and critical. Third, this was a single-center study, which should be validated by a multi-center study. In addition, our study had a relatively small number of death events, which might be unpowered to achieve statistically significant results between early and delayed endoscopy groups.In conclusion, our study did not confirm an association of timing of endoscopy with risk of 5-day failure to control bleeding or in-hospital death in patients with cirrhosis and AVB. Endoscopy after adequate medical therapy may be more effective than urgent endoscopy. RCTs with strict eligibility criteria and optimal definitions regarding timing of endoscopy are needed to confirm the effect of the timing of endoscopy on prognosis of patients with cirrhosis and AVB in the future.Below is the link to the electronic supplementary material.Supplementary Material 1


The discovery of proteins that neutralise vascular endothelial growth factors, such as pegaptanib, ranibizumab and aflibercept, can inhibit the process of angiogenesis, thereby restoring eyesight in individuals with retinal vascular disorders. However, due to the posterior location and chronic nature of retinal diseases, a safe and effective intraocular protein delivery system is currently lacking. Thus, dissolving bilayer microneedles (MNs) with the potential to deliver proteins to the back of the eye in an efficient and minimally invasive manner were developed in this study. A model protein, ovalbumin (OVA), was incorporated into MNs fabricated from different polymers, including hyaluronic acid (HA), polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Optimised PVA/PVP MNs were demonstrated to be robust enough to pierce porcine sclera with > 75% of the needle length penetrating the sclera and dissolving within 150 s. SDS-PAGE and OVA-specific ELISA revealed that the bioactivity of the model protein was maintained during the manufacture of MNs. In hen’s egg-chorioallantoic membrane test, MNs fabricated from all chosen polymers were classified as non-irritants. Furthermore, ex vivo permeation studies showed that optimised MNs could permeate 86.99 ± 7.37% of OVA through the sclera, twice that of the needle-free patch (42.16 ± 3.95%), highlighting the capability of MNs to circumvent physical barriers and promote protein delivery to the posterior segment of the eye. In this work, a novel, efficient and safe intraocular protein delivery system was successfully established. Retinal diseases such as macular degeneration, retinal detachment and diabetic retinopathy are leading causes of irreversible blindness in developed countries and significantly impact the individual patient’s quality of life . VariousCurrently, the mainstream route of protein administration to the back of the eye is intravitreal (IVT) injection. It has the advantages of bypassing ocular barriers and delivering macromolecules directly to the vitreous humour, thereby providing precise, immediate and effective treatment . AlthougAs a convenient, easily administered and minimally invasive device, microneedle (MN) has emerged as a reliable choice for transdermal and intraocular administration –10. So f–7 cm2/s compared with 6.70 × 10–7 cm2/s) [This work aims to develop and optimise dissolving MNs to provide an effective and patient-friendly option for the intraocular delivery of biomacromolecules. For this purpose, ovalbumin (OVA) was selected as a model protein for the typical anti-vascular endothelial growth factor (VEGF) drug ranibizumab because of their similar molecular weight (44 kDa compared with 48 kDa), hydrodynamic radius (5.8 nm compared with 5.5 nm), denaturation temperature (80 °C compared with 75 °C) and diffusion coefficient (7.76 × 107 cm2/s) . FurtherAlbumin from chicken egg white lyophilised powder , bovine serum albumin (BSA), phosphate-buffered saline  tablets, sodium chloride (NaCl) and PVA (31–50 kDa) were purchased from Sigma-Aldrich . HA  was obtained from Kewpie Corporation . PVP K-29/32 (58 kDa) and K-90 (360 kDa) were purchased from Ashland . Glycerol, AnalaR NORMAPUR, 99.5% was obtained from VWR International . All other chemicals were of analytical reagent grade.The fabrication of OVA-loaded dissolving MNs was divided into two main steps. Initially, aqueous blends of selected polymers were prepared and mixed with an appropriate amount of OVA. A 30% w/w stock of PVA 31–50 kDa was prepared by adding the required mass of PVA to water and then kept in an oven at 80 °C overnight until a clear gel formed. A 40% w/w aqueous solution of PVP K-29/32 was prepared by adding the required mass of PVP into deionised water and then stirring until a clear gel formed. A mixture of 15% w/w PVA and 20% w/w PVP was prepared by mixing the stock solutions of PVA and PVP in a ratio of 1:1. A 2.5% w/w stock solution of HA was fabricated by adding the required quality of HA to deionised water, followed by sonicating for 30 min to dissolve the HA. Subsequently, aqueous blends of selected polymers were mixed with the OVA aqueous solution. The compositions of the formulations prepared are listed in Table Following the preparation of the pre-formed dry baseplate and drug-contained stock gels, 10 µL of the polymeric blend was accurately transferred onto a laser-engineered silicone conical mould  using a positive-displacement pipette . The pre-formed dry baseplate was then placed on the back of the polymeric blend. Subsequently, the moulds were placed in a positive pressure chamber  and a positive pressure of 5 bar was applied for 15 min to force the gel to fill the mould microprojections. The MNs were then dried at room temperature for 24 h and carefully removed from the mould. The manufacturing process of OVA-loaded MNs is shown in Fig. BC is the height before compression and HAC is the height after compression.The mechanical test of prepared MNs with and without OVA was carried out using a TA-TX2 Texture Analyser , as described previously with slight modifications , 33. BriThe insertion study of the developed MNs was carried out using the Texture Analyser set-up shown in Fig. The dissolution of blank and OVA-loaded bilayer MNs formulated from different polymers was investigated in situ in excised porcine scleral tissue, as described previously . In brieIn order to quantify the amount of OVA in the needle-part of each MN, the baseplate of the MN was held by a customised device and only the needle part was immersed in 2 mL of PBS (pH = 7.4) until all needles were dissolved. After complete dissolution, the sample was further diluted with PBS (pH = 7.4) and analysed by the ELISA method described in "3, 152 µL formaldehyde and 200 mL deionised water) for 25 min. After that, the gel was rewashed with water to remove silver nitrate. The gel was then incubated with gel developer solution until the desired level of staining was acquired. Finally, the gel was transferred to gel stop solution and then the image was taken.The stability of OVA released from the MNs formulated with different polymers was evaluated using SDS-PAGE. Initially, MNs were dissolved in PBS (pH = 7.4) and then 12 µL of NuPage® LDS sample buffer was added to 8 µL of dissolved MN solution. The samples were boiled at 70 °C for 10 min and then cooled to ambient temperature. Additionally, native OVA and fully reduced OVA were analysed and recorded as negative and positive controls, respectively. A NuPage® 4 to 12%, Bis–Tris, 1.5 mm, 10-well gel was rinsed three times using the running buffer (50 mL NuPage® and 950 mL deionised water) and placed in the XCell Surelock™ Mini-Cell gel running tank. Afterwards, 10 µL of each MN sample, control and diluted protein molecular weight marker (ladder) were loaded into each well of the gel. Samples were run for approximately 50 min at 200 V constant voltage and 220 mA maximum current, after which the gel was removed. Before putting in the gel fixer solution, the gel was rinsed with deionised water. After fixation, the gel was washed three times with a gel washer solution composed of methanol and deionised water. The gel was then incubated with cold silver nitrate solution  and blocking buffer was prepared by dissolving 1% w/v BSA in washing buffer. After the preparation of reagents, 100 µL OVA samples and standards were coated into each well of a high-binding 96 well-plate and incubated overnight at 4 °C. The plate was then washed three times with 200 µL washing buffer to remove unbound OVA. Next, 200 µL of blocking buffer was added to each well to block the sites uncoated by OVA. After incubating for 20 min at room temperature, the plate was rewashed with washing buffer. The anti-OVA polyclonal antibody conjugated with biotin was diluted at 1:5,000 in blocking buffer and pipetted into each well in a volume of 100 µL. After 40 min incubation, washing was carried out three times as performed previously. The plate was incubated with the enzyme streptavidin–horseradish peroxidase diluted 1:10,000 in PBS (pH = 7.4) for 30 min and then washed with washing buffer. 100 µL of 3,3',5,5'-tetramethylbenzidine (TMB) was pipetted into the plate and incubated for 40 min under protection from light. Finally, a microplate reader  was used to evaluate the optical density at 650 nm.t-test and one-way ANOVA by using GraphPad Prism® version 8 . In all circumstances, a difference was considered to be statistically significant when the p-value was less than 0.05 and probability value were recorded as * = p < 0.05, ** = p < 0.01 and *** = p < 0.001. Data are presented as means ± standard deviation (SD) of the mean from triplicate measurements.In this work, we compared two and more groups using Student’s In this investigation, OVA was used as a model protein to investigate the capability of MNs composed of different polymers to deliver the therapeutic macromolecules to the posterior segment of the eye. Selected polymers for casting dissolving MNs included PVA, PVP and HA, which have previously been demonstrated to be biodegradable, biocompatible and effective for ocular drug delivery , 24. Tabp > 0.05) difference between blank MNs and OVA-loaded MNs, suggesting that the incorporation of OVA was unlikely to adversely affect the MN robustness. Furthermore, after compression, the baseplate utilised to hold the MN needles was found to maintain its original shape and no cracks were observed, indicating that the pre-formed baseplate had sufficient mechanical strength to withstand the compression.To ensure effective ocular drug administration, the developed MNs need to be sharp and strong enough to withstand the compression without breaking and be successfully inserted into the scleral tissue. Additionally, the incorporation of biomacromolecules may have either a weakening or a strengthening influence on the MN . TherefoDifferent from the compression test, the insertion study was carried out using excised porcine scleral tissue. As shown in the OCT images of various MNs inserted into the sclera Fig. A, there In order to determine the optimal time required to apply the fabricated dissolving MNs on the scleral tissue, dissolution studies of MNs composed of various polymers before and after OVA loading were carried out. Figure The purpose of this investigation was to develop a polymeric dissolving MN that can be used to load and deliver bioactive biomacromolecules to the back of the eye. Thus, it is essential to determine the stability of the OVA after being loaded into MNs. In this study, the MNs composed of various polymers were dissolved in PBS (pH = 7.4), after which the aqueous solution of the MN was withdrawn and analysed by SDS-PAGE. OVA not incorporated into the MN (free OVA) and fully reduced OVA were selected as the negative and positive controls, respectively, to show how the fragmentation pattern changes as OVA stability is compromised.Figure p > 0.05), confirming the stability of OVA in these selected polymers. The results of ELISA were further underpinned by the findings of SDS-PAGE, whereby the manufacturing process of the bilayer MN and the incorporation of chosen polymers was shown to be harmless to the protein.Upon drying, the amounts of OVA in each PVA, PVP, PVA + PVP and HA MN array determined by ELISA were 105.66 ± 11.74, 110.96 ± 9.66, 94.52 ± 15.04 and 88.34 ± 13.12 µg/array, respectively. The difference between the amount of OVA recovered from each MN array and its initial addition (100 µg/array) was insignificant (p < 0.01). Leading on from these results, the selected HA was excluded from the candidate polymers for fabricating ocular dissolving MNs, whereas PVA, PVP and their mixture were recognised as better choices.The permeation study of OVA-loaded dissolving MNs was conducted using the Franz-diffusion cells set-up to ensure that the prepared MNs can penetrate the scleral tissue and deliver the drug to the posterior segment of the eye. Permeation profiles of MNs fabricated from selected compounds are shown in Fig. p < 0.001) enhance the %cumulative permeation of OVA in the receptor chamber from less than 30% to 87%.Subsequently, the PVP MN was selected as the model MN and compared with conventional routes of administration, including 50 μL eye drops and needle-free patches with the same composition as the OVA-loaded PVP MNs. The results are presented in Fig. Due to the delicate nature of the eyes, for drug delivery systems utilised to treat eye disorders, it is necessary to study the irritating potential of the formulation before testing in preclinical animal models. Accordingly, the eye irritation potential of the OVA-loaded dissolving MNs formulated from PVA, PVP, PVP + PVA and HA was determined using the HET-CAM test. The functional vasculature of the chicken placenta is used in this assay to simulate the ocular condition in vivo . VersatiDue to the high invasiveness of conventional hypodermic needles and the requirement for frequent administration, IVT injection, which is the mainstay of treatment for retinal diseases, can potentially lead to devastating adverse effects. As a minimally invasive device, dissolving MNs can be an intelligent alternative to the conventional hypodermic needle and circumvent its aforementioned limitations. Anti-VEGF-based therapies are regarded as the first-line therapy to suppress neovascularisation and defend against retinal vascular disorders . Commonl., in the MN cast by the one-step centrifugal method, only 2% of the drug was localised in the needle part, whereas the majority of the drug (> 70%) was extracted from the baseplate layer [Previous work from our group has described the preparation of dissolving MNs loaded with fluorescein isothiocyanate–dextran with molecular weights of 70 kDa (FD70) and 150 kDa (FD150) by a one-step centrifugal casting approach . The prete layer . This obte layer , two-steIn addition to the manufacturing approach, the choice of polymer is also critical in the formulation of the MN. The selected polymer must be sufficiently robust, rapidly dissolving, biodegradable and biocompatible. Therefore, in this investigation, several polymers were selected, including PVA, PVP and HA, which have been proven to be well tolerated in the eye and are widely used in ophthalmic drug delivery , 34, 35.p > 0.05), indicating the casting procedure and selected matrix materials were compatible with the incorporated protein. Overall, these findings demonstrate the stability of OVA in chosen polymers and the viability of these MNs as vehicles for biomacromolecules administration.In order to determine the potential of the developed dissolving MNs to effectively deliver biomacromolecules to the posterior segment of the eye, a variety of parameters were evaluated, including the morphology, mechanical strength, scleral penetration, dissolution kinetics and permeation profile of MNs, as well as the stability of the incorporated protein. Furthermore, a key consideration in dissolving MNs developed for biomacromolecule administration is their ability to maintain the stability of incorporated proteins. In this investigation, the stability of OVA within different MNs was evaluated by SDS-PAGE and ELISA. As displayed in the results of SDS-PAGE, compared with free OVA, no discernible variations were observed in OVA released from the prepared MNs, suggesting that no degradation or aggregation occurred. The amount of OVA in each MN quantified by ELISA (> 88 µg/array) was in close agreement with the amount of OVA initially added (100 µg/array) (The Franz-diffusion cell set-up was used to study the ex vivo permeation profile of OVA-loaded MNs. OVA-loaded MNs composed of various polymers were applied to excised porcine scleral tissue at a force of 3 N/array and their ability to deliver the drug across the sclera was evaluated by analysing the amount of OVA recovered from the receptor chamber. Herein, OVA-specific ELISA was used to quantify OVA, since it can not only distinguish OVA from interfering proteins adhering to porcine scleral tissue but also specifically count the amount of bioactive OVA. Compared with the other three formulations, MNs made of HA had the lowest permeation profile and could only deliver less than 40% OVA across the porcine sclera. This is unsurprising, as mechanical tests proved that HA MNs exhibited poor mechanical strength with more than 30% height reduction after compression. Furthermore, the insertion study highlighted the limited insertion capability of HA MNs. As evidenced by previous investigations, only drugs localised to the part of MN arrays inserted into biological tissue could be available for delivery , 46. In In order to investigate the ocular delivery efficiency of MNs and conventional administrations, PVP MN was selected and compared with the permeation profiles of eye drops and needle-free patches composed of the same constituent. Following the application via the conventional routes, only less than 40% of OVA could be recovered from the receptor chamber, which was less than half of the amount of OVA permeated by PVP MNs. Given the dense connective nature of scleral tissue , 48, it The protein-loaded bilayer MNs designed in this investigation enable the self-administration of biological macromolecules to treat retinal diseases. Unlike conventional hypodermic needles that require trained medical staff and often cause discomforting eye reactions, this novel device is easy to handle and user-friendly. Protein waste can be eliminated as the therapeutic molecules are specifically concentrated in the needle-part. Moreover, the developed OVA-loaded MNs were demonstrated to be safe for ocular administration and could significantly promote the permeation of biomacromolecules through the scleral tissue. Accordingly, the designed device provides a convenient and less invasive choice for the intraocular administration of biomacromolecules.In this investigation, the protein-loaded dissolving bilayer MN was successfully developed to facilitate the transscleral delivery of biomacromolecules. The pre-formed baseplate and positive pressure were used to concentrate the protein in the needle-part to reduce loss of protein. The protein released from MNs manufactured via this approach was demonstrated to be bioactive by conducting SDS-PAGE and ELISA. Furthermore, several biodegradable and biocompatible polymers were screened for MN fabrication and characterised for mechanical strength, insertion depth, dissolution kinetics and permeation profiles. Based on these evaluations, PVP, PVA and the mixture of PVA and PVP were revealed to be suitable for casting MNs with excellent physical properties and sufficient intraocular delivery efficiency. The ex vivo permeation studies demonstrated that the introduction of MNs enabled rapid and efficient delivery of the protein to the posterior segment of the eye. In conclusion, the developed protein-loaded bilayer MNs provide a novel and promising option for treating retinal disorders in an effective and minimally invasive manner.


UFT is applied as an optical and dielectric modifier for bisphenol A epoxy resin (DGEBA), and UFT epoxy composites with high transmittance (>80%), tunable haze (45–58%) and excellent dielectric properties can be prepared at low UFT contents (0.5–1 wt%), which delivers an optimal design for dielectric encapsulation systems with efficient light management in solar cells. Additionally, UFT epoxy composites also show excellent UV blocking, and hydrophobic, thermal and mechanical properties. This work provides a template for the synthesis of covalent bond‐mediated nanofillers and for the modulation of haze and dielectric properties of dielectric encapsulation materials for energy systems, semiconductors, microelectronics, and more.Dielectric encapsulation materials are promising for solar cell areas, but the unsatisfactory light‐management capability and relatively poor dielectric properties restrict their further applications in photovoltaic and microelectronic devices. Herein, an interface fusion strategy to engineer the interface of MOF  and simultaneously enhanced dielectric properties, which show promising applications in solar cells. Previous studies revealed that optical materials with high transmittance and high haze can improve light absorption by increasing the path of scattered light through the active solar layers, thereby enhancing the short‐circuit current (Isc) and power conversion efficiency (PCE). Nevertheless, the realization of epoxy thermosets with high transmittance and high haze as the light managers of solar cells is still in its infancy. In addition, low dielectric and insulating properties of encapsulation materials also play an important role in the field of photovoltaic devices, semiconductors, and microelectronics. Therefore, it is of great significance and remains an ongoing challenge to develop dielectric epoxy encapsulation materials combining high light transmission and high haze.Epoxy thermosets are one kind of the commonly used encapsulation materials for solar cells due to their high transparency, heat resistance, and excellent mechanical properties.1 Howe2, alumina nanowire, and nanocellulose) have been utilized to improve the haze and scattering ability of matrices. Among them, metal‐organic frameworks (MOFs) were employed as scattering media for the preparation of optical materials with high transmittance and high haze, indicating their potential application in the light managers of solar cells. Besides, MOFs are also promoted as next‐generation low dielectric materials due to the porosity and insulation. Hence, MOFs show great potential for the preparation of dielectric light diffusers. As one of the most stable and versatile MOFs, UiO‐66‐NH2 is widely applied in gas adsorption, catalysis and drug delivery. However, to the best of our knowledge, no studies have been conducted on applying UiO‐66‐NH2 to the light management of solar devices. Nevertheless, the exposed pore structure of UiO‐66‐NH2 is also susceptible to the penetration of small molecules , which destroys the porosity and changes the optical properties , thereby impairing dielectric property and scattering ability. Furthermore, previous studies usually introduced MOFs directly into polymer matrices to prepare low dielectric materials, which may lead to the poor interfacial compatibility and large interfacial polarization. Therefore, reliable strategies are required to achieve efficient light management and maintain the excellent dielectric property of UiO‐66‐NH2.Various nanofillers  is self‐assembled by 6FDA‐TFMB and several particles of UiO‐66‐NH2. With the aid of the interface fusion strategy, 6FDA‐TFMB acts as a linker to enlarge the particles of UFT to several hundred nanometers, which leads to the significant forward scattering according to Mie scattering theory. It is worth noting that the unique core–shell structure of UFT also protects UiO‐66‐HN2 from penetration by small molecules, ensuring the high porosity of UiO‐66‐HN2 and maintaining the disparity in the optical properties between the matrix and UFT. Furthermore, the anhydride groups on the UFT surface also promote the compatibility between UFT and epoxy matrix, which is essential for the formation of uniform haze in optical materials and the reduction of interfacial polarization in dielectric materials. Therefore, UFT is applied as an optical and low dielectric modifier for bisphenol A epoxy resin DGEBA , II (1730 cm−1), III (1383 cm−1) and IV (720 cm−1), meanwhile there does not exist any amino stretching vibration, proving the complete imidization. Furthermore, the anhydride characteristic peaks appear at 1860 and 1790 cm−1, indicating that 6FDA‐TFMB is anhydride‐terminated. The appearance of Zr—O and imide absorption peaks for UFT manifests that 6FDA‐TFMB has been successfully encapsulated on UiO‐66‐NH2. It is noteworthy that the amino characteristic peaks do not disappear completely, owing to the large molecular weight of 6FDA‐TFMB that only reacts with NH2 on the surface of UiO‐66‐NH2 framework. Therefore, the molecular weight of 6FDA‐TFMB is also investigated by gel permeation chromatography  is about 5.2 × 103 g mol−1. Compared with tiny pores of UiO‐66‐NH2, such a large molecule could not enter the interior of UiO‐66‐NH2, ensuring its high porosity, which is in conformity with the FT‐IR results, that is only the reaction between 6FDA‐TFMB and NH2 on the surface of UiO‐66‐NH2. Besides, X‐ray diffraction  is also employed to assess their thermal stability  and residual char are illustrated in Table 2 exhibit the high thermal stability due to their rigid structures . Combining their merits, UFT also shows high Td 5% (325.7 °C) and residual char (55.3%). Figure 2 adsorption–desorption isotherms of UiO‐66‐NH2 and UFT, the BET surface area of UiO‐66‐NH2 is 1039 m2 g−1, which is similar to the results of previous studies, while the BET surface area of UFT decreases to 715 m2 g−1 due to the non‐porous 6FDA‐TFMB on the surface of UFT. The elemental compositions of UiO‐66‐NH2 and UFT are tested by XPS  between the matrix and UFT. Besides, the terminal anhydride groups of 6FDA‐TFMB can covalently bond the epoxy groups and promote the dispersion of UFT in the polymer matrix, which is significant for the preparation of optical materials with uniform haze. Additionally, Figure 2 (UiO‐0.5), are prepared and their optical properties are compared with those of UFT‐0.5. 6FDA‐TFMB shows good compatibility with epoxy resin due to its suitable molecular weight and large volume of —CF3 side group, thus 6FT‐0.5 possesses high transmittance  at 500 nm Figure 2a, whichno group.17 Hazs Figure . CompareJ–V measurements, this strategy has the same effect as increasing the illumination light intensity. Theoretically, light intensity increase will lead to the direct increase in Jsc  and the slight increase in Voc , which eventually leads to an increase in PCE. To verify this conjecture, UFT composites with various UFT loadings are adhered to the silicon‐based solar cells and their PCE are investigated  cells is less efficient in the light capture capability than the pyramidal‐shaped light trapping structure generated by alkali in monocrystalline silicon cells, resulting in inferior PCEs. Therefore, the light trapping capability of mc‐Si cells needs to be further improved. Previous reports have revealed that various nanostructures are promising in improving the light trapping by increasing the light path, but most of which are not based on silicon cells. Here, UFT composites are applied to mc‐Si cells as encapsulation materials Figure  with the2.3εr) and dielectric loss tangent (tanδ) of the UFT epoxy composites are measured from 1 to 100 MHz. It is found that the εr , respectively, as compared to those (3.45 and 0.021) of UFT‐0. In addition, the dielectric properties of UFT‐0 and UFT‐0.8 are also tested in the range of 9–12 GHz. As revealed in Figure δ of UFT‐0.8 at 10 GHz is decreased from 0.023 (UFT‐0) to 0.018. These results are attributed to the unique core–shell structure of UFT through interface fusion strategy. Not only does UFT combine the high porosity of UiO‐66‐NH2 (εr = 2.0 at 1 MHz) and the low dielectric fluorine‐containing imide oligomer 6FDA‐TFMB (εr = 2.8 at 1 MHz), but also 6FDA‐TFMB on the surface of UFT can prevent small molecules from the penetration into UFT, ensuring the high porosity of UiO‐66‐NH2. In addition, according to the epoxy curing mechanism, the reaction of amino groups and epoxy groups will generate high polar hydroxyl groups, which is detrimental to the improvement of dielectric properties, and an effective way is to replace amino curing agents with anhydride  of 6FDA‐TFMB. As a strong polar molecule, water possesses a very high εr (about 78) and influences enormously the dielectric properties of the materials, thus it is very crucial to assess the hydrophobic properties of UFT‐modified epoxy thermosets. Figures 3).Dielectric property is another important parameter of encapsulation materials, and the dielectric constant εr and dieδ Figure  of the e2.4Td 5% and residual char (R at 700 °C) than UFT‐0. When the UFT content is 0.8 wt%, the Td 5% and R of UFT‐0.8 reached 380.0 °C and 10.3%, which is ascribed to the high thermal stability and residual char of UFT. While higher UFT content (1 wt%) may be detrimental to Td 5%, probably due to the agglomeration of UFT particles and the decrease in crosslink density of the epoxy thermosets, which is consistent with the results of the previous works. In addition, the mechanical properties of the UFT composites are also investigated , mainly owing to: i) the rigid structure of UiO‐66‐NH2 not only facilitates the enhancement of tensile strength, but also provides blocking and dispersing effect on crack expansion during the fracture of the thermosets, which is known as “crack pinning”, and thus enhances the toughness; ii) the anhydride‐terminated 6FDA‐TFMB on the surface of UFT is chemically bonded with the epoxy groups to increase the compatibility of UFT and epoxy matrix, which is also conducive to the enhancement of mechanical properties; and iii) UFT optimizes the crosslink density of the epoxy thermosets to increase the toughness. However, higher UFT loading induces an agglomeration effect and thus deteriorates the mechanical properties, which is analogous to the thermal properties. Moreover, the fracture morphology of UFT‐modified epoxy thermosets after impact measurement is observed by scanning electron microscope (SEM) , impact toughness, and tensile strength of UFT epoxy composites and pure epoxy thermosets. UFT epoxy composites show excellent overall performance  compared to that of pure epoxy thermosets. To further demonstrate the performance advantages of UFT epoxy composites, Table Encapsulation materials also require excellent thermal and mechanical properties to provide protection for the devices. Therefore, the thermal properties of the epoxy thermosets with different UFT contents are tested by TGA  Figure . The fra3In this paper, we design a novel MOF cluster with enhanced forward scattering and robust porosity through interface fusion strategy, and employ it to prepare UFT epoxy composites with high transmittance (>80%), tunable haze (45–58%) and improved dielectric properties. UFT epoxy composites show efficient light management, resulting in a significant enhancement in PCE of silicon solar cells. In addition, UFT epoxy composites also possess excellent anti‐UV, hydrophobic, thermal, and mechanical properties. Therefore, UFT composites are promising for encapsulation materials in energy systems and microelectronics industries. The concept of assembling nanoparticles into cluster structures through engineering and fusing their interfaces provides a novel and facile approach for the synthesis of covalent bond‐mediated multifunctional nanostructures as well as the simultaneous achievement of efficient optical management and excellent dielectric properties in encapsulation systems.44, 98%) and 2,5‐dicarboxyaniline  were obtained from Aladdin Reagent Co., Ltd., China. 4,4″‐(hexafluoroisopropylidene)diphthalic anhydride , 2,2″‐bis(trifluoromethyl)benzidine , methylhexahydrophthalic anhydride , and 2,4,6‐tris(dimethylaminomethyl)phenol  were purchased from Beijing InnoChem Science & Technology Co., Ltd. Diglycidyl ether of bisphenol A  with the epoxy value of 0.51 was supported by Baling Petrochemical Co., Ltd., China. 6101 (A/B) Epoxy resin  was provided by TONSIN LIDA Co., Ltd., China. Tempered glass (thickness of 1 mm) was supported by Merck Co., Ltd., USA. N,N‐dimethylformamide , acetic acid , benzoic acid (99.5%), toluene (99.5%), n‐hexane (97%), methanol (99.5%), and dichloromethane  were supplied by Richjoint Co., Ltd., China.Zirconium chloride (ZrCl4 (0.350 g), BDC‐NH2 (0.272 g), DMF (140 mL) and HAc (5.15 mL) were added to the hydrothermal kettle, then sonicated until the solution was clarified and placed in an oven at 120 °C for 24 h. The precipitate was washed 3 times with DMF to remove excess reactants and centrifuged at 10 000 rpm for 10 min, followed by being washed with methanol to remove residual DMF. UiO‐66‐NH2 was obtained after being dried in vacuum at 100 °C for 24 h.ZrCln‐hexane. The precipitate was filtered, washed twice with n‐hexane, dried in vacuum at 120 °C for 1 day, and 6FDA‐TFMB was obtained.6FDA (5.331 g), benzoic acid (17.5 g), and HAc (50.0 mL) were added to a three‐neck flask and stirred at 120 °C for 1 h under nitrogen. Then TFMB (2.562 g) was added and the mixture was stirred at 120 °C for 5 h. After the reaction was completed, the product was cooled to room temperature and precipitated using 2 (0.5 g), anhydride‐terminated 6FDA‐TFMB (6.5 g) and DMF (60 mL) were added to a three‐neck flask and sonicated until UiO‐66‐NH2 was well dispersed, followed by a reaction at room temperature for 72 h under nitrogen, then toluene (10 mL) was added and the suspension was refluxed at 120 °C for 24 h. After cooling to room temperature, the suspension was centrifuged, and the precipitate was washed twice with DCM to remove the unreacted 6FDA‐TFMB, dried under vacuum at 120 °C for 24 h, and UFT was obtained.UiO‐66‐NH2 were merged on a printed circuit board (PCB) and encapsulated with UFT composites. The schematic diagram of preparation process of UFT composites is illustrated in Figure The formulation of UFT‐modified epoxy thermosets is displayed in Table The authors declare no conflict of interest.M.H.W. and W.Q.X conceived the ideas and designed the experiments. M.H.W, J.X.L., and X.Z. performed the experiments. All authors discussed the results and contributed to writing the paper.Supporting InformationClick here for additional data file.


As a result of optimizing the thicknesses of each type of unit layer, low-temperature 400 nm thick IZO multilayers with excellent transparent electrode quality, indicated by the low sheet resistance (R ≤ 8 Ω/sq.) with high transmittance in the visible range (It is common knowledge that using different oxygen contents in the working gas during sputtering deposition results in fabrication of indium zinc oxide (IZO) films with a wide range of optoelectronic properties. It is also important that high deposition temperature is not required to achieve excellent transparent electrode quality in the IZO films. Modulation of the oxygen content in the working gas during RF sputtering of IZO ceramic targets was used to deposit IZO-based multilayers in which the ultrathin IZO unit layers with high electron mobility (μ-IZO) alternate with ones characterized by high concentration of free electrons ( Transparent conductive oxide (TCO) thin films are characterized by high electrical conductivity and high optical transmission in the visible range of the spectrum. A TCO-based transparent electrode (TE) is an integral part for many optoelectronic devices  ,2,3,4. TModern trends in the development of the industry lead to the emergence of new, more stringent requirements for both properties of thin-film materials and technological routes for their formation. In particular, for the further wide use of the TCO materials as TEs, it is urgent to find a solution to the “contra-indicated requirement”—the achievement in TCO films of the required specifications of low resistance and high transparency at the lowest possible process temperature ,9.All this causes a continuous search for new materials with properties close to those of the “perfect” TE ,11,12 as2O3, ZnO, SnO2 and their compositions, there are performance limits of the TCO films that are determined solely by the electron density in the films. In particular, there is a well-defined limit to the achievable mobility resulting from the electron scattering, regardless of the oxide system or the preparation method used. Experimental data show that this limit is now regularly approached  MLs was 200 min. Taking into account that the growth rates of n-ZnO and µ-ZnO films were the same (~2 nm/min), the thickness of all MLs was equal to ~400 nm, regardless of the program for changing the composition of the working gas.The total deposition time for each of the SR of the IZO-based MLs was measured by using a four-point technique , while electrical transport properties were characterized from Hall effect measurements at room temperature by using the van der Pauw geometry  MLs. Moreover, in this experiment, the durations of IZO sputtering in Ar gas and Ar/O2 gas mix were the same, so the following equality was valid for thicknesses of the n-IZO and µ-IZO unit layers forming MLs:nd–IZO and dµ–IZO are the thicknesses of n-IZO and µ-IZO unit layers, respectively, D is the total thickness of the ML, N is the number of the (n-ZnO/µ-ZnO) unit pairs.A systematic investigation was conducted firstly varying the [n-ZnO/µ-ZnO] unit pair thickness in 400 nm thick N × [n-ZnO/µ-ZnO] MLs with N of 200, 100, 40, 20 and 10 were deposited, in which nd–ZnO and dµ–ZnO were 1, 2, 5, 10 and 20 nm. n and resistivity ρ as a function of the number of unit pairs N in the N × [n-IZO/µ-IZO] MLs. For comparison, dashed lines in n values for ~400 nm thick single-layer homogeneous IZO films, obtained under stationary conditions of the working gas supply, at an oxygen content in the working gas of 0 (dashed black), 0.2 (dashed blue) and 0.4% (dashed red)  working gas  gas mix. A further increase in N to 200 results in an abrupt drop in μ to the value of 36 cm2/V·s, which corresponds to the value for the homogeneous IZO film deposited in the Ar/O2(0.2%) gas mix.At the same time, the Hall mobility μ exhibits a significant dependence on the number of unit pairs N from 10 to 100 results in the fact that the resistivity ρ of the N × [n-IZO/µ-IZO] MLs has an opposite tendency to fall for this range of N  and μ-IZO layers (with lower carrier concentration) is determined by the following expression:nn–IZO and nµ–IZO are the carrier concentrations of n-IZO and µ-IZO unit layers, respectively.The insensitivity of N. Therefore, n is the arithmetic mean of nn-IZO and nµ-IZO:Taking into account equality (1), expression (2) takes a simpler form, confirming that the total concentration in MLs with equal unit layer thicknesses does not depend on N can be explained by the fact that some of the free carriers from the interfaces of the donor-rich n-IZO unit layers move to the adjacent regions of the high-mobility μ-IZO layers  ML, consisting of 400 IZO unit layers with a predicted thickness of 1 nm, can be explained by the inertia of the two-channel gas supply system. In fact, this ML differs little from a homogeneous IZO film deposited in the Ar/O2(0.2%) gas mixture.At the same time, the observed features of μ dependent on O layers ,22,23,24n-IZO unit layer, enriched with oxygen vacancies, at a constant thickness of a highly mobile μ-IZO unit layer (dµ–IZO = 2 nm) on the electrical characteristics of MLs composed of these layers was additionally studied. Obviously, in the ML the total concentration of charge carriers n should increase with an increase in nd–IZO at constant dµ–IZO = 2 nm. However, this reduces the number of pairs N in the ML (as well as number of n-IZO/µ-IZO interfaces) too. Indeed, with an increase in nd–IZO, there are tendencies of an increase in n and a decrease in µ , while the Hall mobility µ decreases by less than 1% (from 39 to 38.7 cm2/V·s). Therefore, for the case of the ML in which nd-IZO = 2 × dµ-IZO = 4 nm, a minimum of resistivity ρ of 2.9 × 10–4 Ω·cm is observed. A further increase in nd-IZO to 12 nm leads to a sharper decrease in µ (by about 30%) against the background of a gradually rising concentration n, which generally results in a trend towards an increase in ρ up to 3.3 × 10–4 Ω·cm.However, it should be noted that when n-IZO layers with thickness values of 2 and 4 nm among the deposited MLs. The first ML based on a repeating [n-IZO2 nm/µ-IZO2 nm] pair is characterized by the highest value of Hall mobility μ of 39 cm2/V·s with ρ = 3.2 × 10–4 Ω·cm. The second optimized ML structure is many stacked [n-IZO4 nm/µ-IZO2 nm] pairs, which demonstrates the lowest resistivity ρ = 2.90 × 10–4 Ω·cm due to the high total concentration (n = 5.55 × 1020 cm–3) and a just a little less Hall mobility (µ = 38.7 cm2/V·s) than that in the former ML structure.Thus, the most interesting from the point of view of the best electrical performance are 400 nm thick MLs formed from alternating 2 nm thick µ-IZO unit layers and 2(0.4%) gas mix medium. At the same time, the MLs are characterized by higher carrier concentration than homogeneous µ-IZO, which is due to the presence of donor-rich n-IZO ultrathin layers in the multilayer structure.It should also be noted that both ML types exhibit Hall mobility values comparable to that observed in a homogeneous highly mobile µ-IZO film obtained by sputtering in an An/O2 in the working gas [N × [n-IZO4 nm/μ-IZO2 nm] and 0.509 nm for N × [n-IZO2 nm/μ-IZO2 nm]. Thus, the microscope studies confirm the improved surface smoothness of the MLs, characteristic for amorphous IZO thin-film materials deposited at low substrate temperatures  and N × [n-IZO4 nm/μ-IZO2 nm]) are shown in n-IZO film. The values of the average optical transmittance The optical transmittance spectra of the optimized 400 nm thick IZO-based MLs (n-IZO film. That can be attributed to the well-known Burstein–Moss shift due to the higher concentration n in both types of MLs compared to that in the homogeneous μ-IZO film  sample and 3.60 eV for the N × [n-IZO4 nm/μ-IZO2 nm]. These values are less than the gE value of the homogeneous n-IZO film (3.63 eV), but greater than gE = 3.51 eV measured for the homogeneous μ-IZO film. The observed gE variation confirms the results of the Hall effect measurements. It can be ascribed to the change in carrier concentration in the IZO homogeneous films and MLs depending on the composition and switching mode of the working gas.In the MLs’ spectra, a significant short-wavelength shift of the fundamental absorption edge relative to the spectrum of the homogeneous µ-IZO film is observed, which leads to a strong increase in transmittance in the short-wavelength region of the visible range (in the neighborhood of 400 nm), similar to that observed in the IZO film . The dirIZO film ,38,39. TThe refractive index dispersion, determined using the pointwise unconstrained minimization approach during the fitting of theoretical transmission spectra with experimental ones , shows an-IZO and µ-IZO, as well as the IZO MLs with optimized structure, by using the generally accepted Haacke’s FOM. It can be seen that the FOM of the optimized MLs is almost twice that of homogeneous IZO films of the same thickness. High TE quality of the MLs is because they simultaneously demonstrate a conductivity behavior similar to the homogeneous n-IZO film deposited in pure Ar and a high transparency characteristic in the visible range, characteristic for homogeneous µ-IZO films deposited in an Ar/O2 gas mix.2 content in the working gas during RF magnetron sputtering of IZO targets were used to form the transparent conducting N × [n-IZO/µ-IZO] multilayer structures. The effect of thicknesses of donor-rich n-IZO and high-mobility μ-IZO unit layers on the electrical properties of the multilayers was investigated. It was found that the electrical characteristics of the multilayers are sensitive to the thicknesses of n-IZO and μ-IZO unit layers. The thickness ranges providing highest mobilities combined with low resistivity were 2 nm for the μ-IZO and 2–4 nm for the n-IZO. Mobility as high as 39 cm2/Vs was achieved for the N × [n-IZO2 nm/µ-IZO2 nm] multilayer with a free carrier concentration of ~5 × 1020 cm−3 and a resistivity of 3.25 × 10−4 Ω·cm. At the same time, with an increase in the thickness of the n-IZO unit layer up to 4 nm, for a comparable mobility in the N × [n-IZO2 nm/µ-IZO2 nm] multilayer, the resistivity was further reduced to 2.9 × 10−4 Ω·cm due to increasing carrier concentration up to 5.5 × 1020 cm−3. As shown by the AFM and SEM measurements, improved surface smoothness, which is typical for amorphous IZO, is also preserved in the electrically optimized multilayers. The combination of donor-rich and high-mobility IZO ultrathin layers in the multilayer structures also improves the optical transmittance towards values inherent in high-mobility μ-IZO films and widens the bandgap towards values characteristic of donor-rich n-IZO films.Programmable periodic changes in the OThus, magnetron sputtering deposition of the multilayer structures based on multiple alternations of the high-concentration IZO and the high-mobility IZO unit layers, achieved by working gas composition cycling during sputtering, can be an effective tool for improving the TE quality of low-temperature IZO-based TCO. The TE quality improvement for the IZO multilayers is apparently associated with some mitigation of the limitations of ionized impurity scattering in them due to the spatial separation of areas with high carrier concentrations and areas with improved carrier transport behavior.


In recent studies, individual scapular anatomy has been found to be related to degenerative full-thickness rotator cuff tears. However, research on the relationship between the anatomical characteristics of shoulder radiographs and bursal-sided partial-thickness rotator cuff tears (PTRCTs) is limited, and the risk factors for this pathology still need to be determined.The bursal-sided PTRCTs group included 102 patients without a history of shoulder trauma who underwent arthroscopy between January 2021 and October 2022. A total of 102 demographically matched outpatients with intact rotator cuffs were selected as the control group. Radiographs were used to measure the lateral acromial angle (LAA), critical shoulder angle (CSA), greater tuberosity angle (GTA), β-angle, acromion index (AI), acromiohumeral distance (AHD), acromial tilt (AT), acromial slope (AS), acromial type, and acromial spur by two independent observers. Multivariate analyses of these data were used to identify potential risk factors for bursal-sided PTRCTs. Receiver operating characteristic (ROC) analysis was performed to assess the sensitivity and specificity of CSA, GTA, and AI for this type of pathology.p = 0.009, 0.200, 0.747 and 0.078, respectively). CSA, GTA and AI were significantly higher in bursal-sided PTRCTs (p < 0.001). LAA, β-angle and AT were significantly lower in bursal-sided PTRCTs. Multivariate logistic regression analysis demonstrated significant correlations between the acromial spur (p = 0.024), GTA (p = 0.004), CSA (p = 0.003) and AI (p = 0.048) and bursal-sided PTRCTs. The areas under the ROC curves for AI, CSA, and GTA were 0.655 (95% CI 0.580–0.729), 0.714 (95% CI 0.644–0.784), and 0.695 (95% CI 0.622–0.767), respectively.The β-angle, AHD, AS and acromion type showed no difference between bursal-sided PTRCTs and controls (Acromial spur, GTA, CSA, and AI were independent risk factors for bursal-sided PTRCTs. Furthermore, CSA was the most powerful predictor of bursal-sided PTRCTs compared to GTA and AI. Rotator cuff tears (RCTs) are a frequent cause of shoulder pain and functional limitations , and theThere is currently a lack of understanding regarding the pathogenesis of RCTs, and some research –5 suggesSeveral anatomical characteristics of the bony structures in the shoulder, such as acromion type , criticaAfter obtaining ethical approval (Review [2019] No. 115), we retrospectively identified 204 patients of our institution between January 2021 and October 2022 to be included in this study. They gave informed consent and, after examination, were divided into two groups. The bursal-sided PTRCTs group consisted of 102 consecutive patients who underwent arthroscopically confirmed isolated bursal-sided PTRCTs. These patients underwent arthroscopy after at least 3 months of ineffective conservative treatment such as nonsteroidal anti-inflammatory drugs, physical therapy, functional exercises, etc. Only patients with available preoperative true anteroposterior  and stanFor the genuine anteroposterior radiograph , the patAccording to Banas et al. , LAA is As reported by Moor et al. , CSA is As reported by Cunningham et al. , The GTAAccording to Maurer et al. , β-angleAs described by Kitay et al.  and AokiAccording to Nyffeler et al. , AI is tGolding et al.  describeThe acromial type was classified according to Bigliani et al. . Type I As described by Biglian et al. , the mosOgawa et al.  describep < 0.05 was considered statistically significant.The SPSS for Windows program  was used for statistical analysis. Continuous variables were expressed as mean ± standard deviation, and categorical variables were expressed as n (%). Shapiro–wilk was used to test whether the data were in accordance with the normal distribution, in which age, CSA, βangle, and AT were in accordance with the normal distribution data, so two independent samples t-test was used. The Mann–Whitney U-test with two independent samples was used for the variables such as LAA, AHD, AS, AI, GTA, and body mass index (BMI), which did not conform to the normal distribution. Categorical variables were tested by the Chi-Square test or Fisher’s exact test. The multivariate logistic regression was used to analyze the parameters related to bursal-sided PTRCT. Inter- and intra-observer measurement reliability was assessed on intraclass correlation coefficient (ICC)  and kappp > 0.05; All demographic data of the patients are listed in p < 0.001). However, the mean CSA was significantly higher in bursal-sided PTRCTs than in the controls . Similarly, the mean AI was significantly higher in bursal-sided PTRCTs than in the controls . For parameters reflecting glenoid inclination, the average values of the β-angle were significantly lower in bursal-sided PTRCTs than in the control group . Besides, we found the average GTA of bursal-sided PTRCTs was significantly higher than that of the control group . Finally, the mean AHD had no significant difference between the two groups .For parameters reflecting a lateral extension of the acromion, the mean LAA values were significantly lower in bursal-sided PTRCTs than in the control group . Additionally, the acromial spur in the bursal-sided PTRCTs group is more common than the control group . For AS, found no difference between groups . Lastly, the most common type of acromion between the two groups remained type II. There was no relationship between acromial morphology and bursal-sided PTRCTs , GTA , CSA  and AI  were significantly associated with bursal-sided PTRCTs (p < 0.01). However, Poor correlations were found between GTA and AI and CSA, acromial spur and the other parameters , CSA (> 32.75°), and GTA (> 71.65°). The area under the ROC curve was highest for the CSA , indicating that the CSA is the most valuable measure for discriminating between the bursal-sided PTRCTs and control groups. The sensitivity of CSA was lower than AI (0.735 vs. 0.863), however, higher than GTA (0.735 vs. 0.608). On the other hand, the specificity of CSA was higher than AI but lower than GTA  and that patients with CSA > 35° are associated with a high prevalence of RCTs. This result was consistent with other studies conducted by Andrade et al. , suggesting that patients with a larger uptilting of the scapula were more likely to develop bursal-sided PTRCTs. Possible causes for this result may include the increasing load on the supraspinatus tendon with increased scapular glenoid inclination because consistently overloading the supraspinatus tendon tends to lead to RCTs , which may be because all cases included were PTRCTs.It is worth noting that some studies have shown a significant association between smoking and RCTs –48. A stFinally, we confirmed the association between larger CSAs and bursal-sided PTRCTs. Additionally, CSA was the most powerful predictor of bursal-sided PTRCTs, with an area under the ROC curve of 0.714, indicating a probability that at least 71.4% of patients with bursal-sided tears have a larger than normal CSA. Similar results were reported by Moor et al. , Pandey This investigation has some limitations. First, this is a retrospective study, and further validation of the results by high-quality randomized controlled clinical trials is needed in the future. Second, photographic and measurement errors could exist despite excellent interobserver agreement. Third, potential selection bias may exist owing to strict inclusion criteria. Finally, since MRI or computed tomography was not used, the accuracy of radiographic measurement was not further verified.Our study revealed that acromial spur, GTA, CSA, and AI were independent risk factors for bursal-sided PTRCTs. Furthermore, CSA was the most powerful predictor of bursal-sided PTRCTs compared to GTA and AI.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by The Second Affiliated Hospital of Nanchang University Medical Research Ethics Committee. The patients/participants provided their written informed consent to participate in this study.JL and SD contributed to the data acquisition. HD, DQ, LL, ML, and JK contributed to data analysis, interpretation, and drafting. JL, ZC, and JT conceived and designed the study. JT were in charge of the conceptualization, supervision, and project administration. All authors read and approved the final manuscript.This work was supported by the Science and Technology Bureau of Nanchang City, Jiangxi Province (2020-NCZDSY-009).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.