Triclosan (TCS), a widely prescribed broad-spectrum antibacterial agent, is an endocrine-disrupting chemical. The relationship and biological mechanisms between TCS exposure and breast cancer (BC) are disputed. We aimed to examine the correlation between urinary TCS exposure and BC risk and estimated the mediating effects of oxidative stress and relative telomere length (RTL) in the above association.2α (8-isoPGF2α), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], and RTL in peripheral blood mononuclear cells.This case-control study included 302 BC patients and 302 healthy individuals in Wuhan, China. We detected urinary TCS, three common oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α, RTL, and BC risk, with the odds ratios  being 1.58 (1.32–1.91), 3.08 (1.55–6.23), 3.39 (2.45–4.77), 3.99 (2.48–6.54), and 1.67 (1.35–2.09), respectively. Continuous TCS exposure was significantly positively correlated with RTL, HNE-MA, and 8-isoPGF2α  but not with 8-OHdG (p = 0.060) after adjusting for covariates. The mediated proportions of 8-isoPGF22α and RTL in the relationship between TCS and BC risk were 12.84% and 8.95%, respectively .Significant associations were observed between log-transformed urinary concentrations of TCS, 8-OHdG, HNE-MA, 8-isoPGFIn conclusion, our study provides epidemiological evidence to confirmed the deleterious effects of TCS on BC and indicated the mediating effect of oxidative stress and RTL on the correlation between TCS and BC risk. Moreover, exploring the contribution of TCS to BC can clarify the biological mechanisms of TCS exposure, provide new clues for the pathogenesis of BC, which is of great significance to improving public health systems. The latest statistics revealed that breast cancer (BC) is the most prevalent cancer  and ranked fifth in terms of cancer mortality worldwide in 2020, according to the International Agency for Research on Cancer (IARC) , a widely used broad-spectrum antibacterial agent, has attracted widespread attention because of its interference with the endocrine system or further cancer induction. Common TCS exposure routes from commercial and healthcare products include the skin and mucous membranes of the oral cavity and the gastrointestinal tract. Consequently, TCS can be measured in human biospecimens, such as urine, milk, and adipose tissue . As a tyBased on previous studies on the effect of TCS on tumorigenesis and development, it has been suggested that TCS is metabolized in the liver by cytochrome P450 (CYP), and this process involves a large number of metabolic processes, such as oxidative stress, cell proliferation, and immune response . To date2α (8-isoPGF2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine, and relative RTL in peripheral blood mononuclear cells. We also estimated the associations between urinary TCS exposure and BC risk and further evaluated the underlying mediating effects of oxidative stress and RTL on the association between TCS and BC risk.In the current study, we determined TCS, three biomarkers of oxidative stress , 0.90 μl of Tel-Reverse-. The HGB reaction consists of 5.00 μl of Power SYBR Green Master Mix, 3.60 μl of RNase-free water, 1.00 μl of gDNA (5 ng/μl), 0.20 μl of HGB-1-, 0.90 μl of HGB-2-. All primers were synthesized by Shanghai Shenggong Bioengineering Co. Ltd. The calibration standard curves ranged in concentration from 0.625 to 10 ng/μl. The flow of the reaction was first 1 cycle at 50°C for 2 min, followed by 40 cycles at 95°C for 3 s, and 60°C for 30 s. Finally, the melting curves were obtained at 95°C for 15 s, 60°C for 1 min, and 95°C for 15 s. To calculate the variability in inter- and intra-plate Ct values, quality control samples were scattered throughout the plates.Relative telomere length, which was calculated by the copy-number ratio between telomeric repeats (T) and a single-copy (HGB) reference gene (S), was determined by Real-Time Quantitative PCR. The T/S ratio (ΔCt) is calculated from the mean telomere cycle threshold (Ct) value minus the mean HGB Ct value. ΔΔCt was calculated by subtracting the ΔCt of the standard sample from the ΔCt of each unknown sample, and then exponentiated  and RTL in the controls, we dichotomized all participants into low- and high-level groups. A logistic regression model was used to assess the associations between TCS, RTL, and oxidative stress biomarkers and BC with odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for age, smoking status, age at menarche, menopausal status, and abortion status, which have been proven to affect the development of breast cancer (β).The concentrations of TCS, 8-OHdG, HNE-MA, 8-isoPGFus study . The vart cancer . PearsonTo evaluate the role of oxidative stress biomarkers and RTL in mediating the correlation between TCS and BC, we used mediation analysis . MediatiX, M, and Y are the exposure to TCS, mediator, and outcome of BC, respectively, while C is a series of covariates. On the basis of the correlation between X and Y (Equation 1), the function—“mediate” in the package—“mediation” is used to analyze the mediating effect of the mediator M between X and Y. The parameter “model.m” is replaced by Equation 2, the parameter “model.y” is Equation 3, the parameter “treat” is the concentration of TCS, the parameter “mediator” is the concentration of each intermediate indicator. The remaining parameters are in the default format. Finally, the analysis outputs the average causal mediation effects (ACME), the average direct effects (ADE), and the proportions mediated (Prop. Mediated) to assess the mediated effects of oxidative stress markers and RTL. The ACME refers to the affection of TCS induces BC through mediating factors, which is complexly combined from Equation 2 and Equation 3, equaling β1 times θ. The ADE refers to the association between TCS and BC adjusted for the mediator, which means the effect is not influenced by mediators. It is equaled to the coefficient β2 in Equation 3. The coefficient β of Equation 1 represents the total effects, that is the influence of independent TCS exposure on BC before adding mediating variable, which consist of the direct effect and indirect effect. The Prop. Mediated refers to the proration of the ACME in the total effects, which represents the extent of mediated effects on the overall effect. Notably, it is necessary to conduct an interaction analysis between exposure and mediators by Equation 4 before mediation analysis. When there was a significant interaction, the parameter “model.y should use Equation 4 instead of Equation 3. Finally, since multiple mediators were of interest, a multiple mediation analysis was conducted by R package-“lavaan,” for exploring the possible effects between mediators on the association of TCS and BC , except for age at menarche (p < 0.05).The basic demographic characteristics of the study participants have been summarized in a previous study . In termp < 0.001). Additionally, BC patients had a significantly longer RTL than the controls (p < 0.001). The median urinary oxidative stress biomarker concentrations  of BC cases were also significantly higher than those of controls .In contrast, the distributions of urinary TCS, 8-OHdG, HNE-MA, 8-isoPGF2α, and RTL in the case-control study were uneven . Notably10-transformed continuous-type urinary TCS concentrations, the elevated TCS dose per unit was attributed to a raised BC risk for 1.58-fold  after adjusting for age, smoking status, age at menarche, menopausal status, and abortion status. When the urinary TCS concentrations were classified into low- and high-exposure groups, individuals with a high TCS exposure level also had a higher BC risk than those with low TCS exposure . Notably, the stratified analysis showed that the risk of breast cancer was higher under certain conditions, such as age > 60 years, age at menarche >13 years, menopause status, and abortion status (We observed significant associations between urinary TCS levels and BC risk in our study population . With lon status .2α were 3.08 (1.55–6.23), 3.39 (2.45–4.77), 3.99 (2.48–6.54), respectively. To better understand the correlation between oxidative stress and BC, individuals were divided into low- and high-concentration groups according to biomarker concentrations. Compared with individuals in the low-concentration groups of the above oxidative stress biomarkers, individuals with a high concentration of HNE-MA, and 8-isoPGF2α also had a higher risk of BC . However, we did not observe a significant relationship between TCS and 8-OHdG levels (p = 0.060). When changing the TCS and other indicators into categorical variables, the results showed similar trends. Although logistic regression analysis did not show a significant association between high-level TCS exposure and high-level 8-OHdG (p > 0.05), other oxidative stress biomarkers still indicated possible differences, reflected by a 1.52-fold or 1.43-fold higher risk compared to low-level exposure and responses. Furthermore, with the increase in each unit in the log10-transformed urinary TCS, the log2-transformed RTL increased by 0.11 (p = 0.001). Likewise, there was an increase in the long RTL group compared to the short RTL group .In the multivariate-adjusted models, the levels of oxidative stress biomarkers and RTL were associated with both TCS exposure and BC risk. Hence, we conducted mediation analyses of oxidative stress biomarkers and RTL in relation to urinary TCS and BC risks . Before 2α and RTL in similar mediation models. The proportion of the relationship between urinary TCS and BC risk mediated in part by 8-isoPGF2α and RTL was 12.84%, and 8.95%, respectively. Finally, the multiple mediation analysis shows no evidence of a significant relationship between 8-isoPGF2α levels and RTL in the mediation of the association between TCS exposure and breast cancer risk  for the publication of any potentially identifiable images or data included in this article.XC and CN performed the statistical analysis and wrote the draft of the manuscript. XC, LF, LW, YL, CN, TD, YC, MZ, ZL, CC, KS, and TY contributed to investigation, resources. RZ, JT, HJL, YZ, and XM contributed to conception and design of the study. All authors contributed to manuscript revision, read, and approved the submitted version.This work was supported by National Key Research and Development Program of China , National Science Fund for Distinguished Young Scholars of China (NSFC-81925032), Key Program of National Natural Science Foundation of China (NSFC-82130098) and Natural Science Foundation of Hubei Province (2019CFA009) for XM; Youth Program of National Natural Science Foundation of China (NSFC-82003547) for YZ; Youth Program of National Natural Science Foundation of China (NSFC-82103929) and Fundamental Research Funds for the Central Universities (2042022kf1205) for JT.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.


Environmental pollution remains one of the most challenging problems facing society worldwide. Much of the problem has been caused by human activities and increased usage of various useful chemical agents that inadvertently find their way into the environment. Triclosan (TCS) and related phenolic compounds and derivatives belong to one class of such chemical agents. In this work, we provide a mini review of these emerging pollutants and an outlook on the state-of-the-art in nanostructured adsorbents and photocatalysts, especially nanostructured materials, that are being developed to address the problems associated with these environmental pollutants worldwide. Of note, the unique properties, structures, and compositions of mesoporous nanomaterials for the removal and decontamination of phenolic compounds and derivatives are discussed. These materials have a great ability to scavenge, adsorb, and even photocatalyze the decomposition of these compounds to mitigate/prevent their possible harmful effects on the environment. By designing and synthesizing them using silica and titania, which are easier to produce, effective adsorbents and photocatalysts that can mitigate the problems caused by TCS and its related phenolic derivatives in the environment could be fabricated. These topics, along with the authors’ remarks, are also discussed in this review. In the next several decades, 68% of the world’s population is expected to live in cities that are highly dependent on water sources affected by agricultural runoffs and industrial and municipal wastewater discharges . TriclosHowever, as of this year, the FDA is not proposing clinical outcome studies for active ingredients when used in healthcare antiseptics or consumer antiseptic rub products. The FDA requires clinical simulation studies for healthcare antiseptics because of ethical concerns with conducting studies in the healthcare setting. The FDA also requires clinical simulation studies for consumer antiseptic rubs because they are intended for use when soap and water are not available. Therefore, they need not demonstrate clinical effectiveness compared to soap and water. Meanwhile, in many other parts of the world, TCS is regulated to not exceed specific concentrations in consumer products such as cosmetic preservatives, textiles, plastics, and adhesives see . This haIn addition to TCS, several other phenolic compounds are used as broad-spectrum antimicrobials, additives in surface cleaners, and precursors for many industrial processes . They include cresols, catechols, bisphenol A (BPA), and nonylphenol ethoxylates. Similar to TCS, these compounds are becoming emerging pollutants because of their widespread use as well as their endocrine-disrupting capabilities. They have thus been listed by various agencies, such as the United States Environmental Protection Agency (US EPA) and the European Union (EU), as pollutants of priority concern. The most notable of these groups of compounds is BPA. Meanwhile, research on nanomaterials with potential applications for environmental remediation has been ongoing over the last several years because these materials have a great ability to adsorb and sometimes photocatalyze various chemical contaminants. For example, inorganic nanomaterials composed of silica and titania can be synthesized with large surface areas to serve as adsorbents of TCS and related phenolic compounds and to minimize or eliminate the negative impacts of these compounds and their derivatives in aquatic environments. Moreover, inorganic materials composed of semiconducting properties, such as titania, exhibit photocatalytic activities to degrade these compounds.TCS is one of the seven most frequently detected phenolic compounds in the streams in the US, with varying concentrations ranging from ng/L to low µg/L ,18. TCS The toxicity of TCS has been studied in numerous animal models, with interest dedicated to its effect on soil and aquatic ecosystem health. TCS has raised concern because high concentrations of this emerging pollutant can disrupt the balance of the ecosystem by killing microalgal species, an essential group of first-step producers in the terrestrial and marine biotopes. For example, TCS pollution has shown the highest sensitivity to algal species ,22,23. TTCS’s mode of action as an antibacterial agent involves diffusion through the cell wall of the bacterial target and disruption of the cytoplasmic membrane, RNA, and lipid and protein synthesis of the bacteria ,26. TCS As mentioned earlier, several other phenolic compounds are ubiquitous in many industrial effluent streams since many of them are used as precursors for the manufacturing of various products ranging from biomaterials to petrochemicals . Not surCurrent techniques used for the removal of these compounds from water include electrochemical oxidation ,32,33,34This article reviews some of the research progress made on the applications of mesoporous inorganic materials for the scavenging and photodegradation of TCS and related phenolic compounds such as phenol and phenol intermediates, which are detrimental to human health and the environment. The article focuses mainly on how adsorption and photocatalysis, as well as their combination, can be applied using mesoporous materials as platforms, with an emphasis on nanostructured silicas and hybrid materials composed of silica and titania, for the removal of these emerging pollutants from the aquatic systems. The unique properties, structures, and compositions of mesoporous nanomaterials suitable for the removal and decontamination of TCS and other phenolic compounds mentioned earlier are highlighted, along with some examples and the authors’ remarks. The examples in the paper are by no means comprhensive but rather illustrative of the points being highlighted. Adsorption is widely used to salvage contaminants including TCS from water systems because adsorption processes are generally simple to design and apply and do not form harmful byproducts . Adsorpt2, TiO2, and ZnO, and carbon-based materials. Most recently, other materials such as layered double hydroxides [The literature is abundant with reports of various (nano)porous materials for adsorbing metal ions, dyes, and pollutants for environmental remediation applications . The mosdroxides  and grapdroxides ,49,50 ha2, TiO2, and carbon-based materials. The creation of mesopores (or nanopores) inside these materials is a necessary step for creating effective adsorbents. These methods can be categorized as hard-templating, soft-templating, and template-free procedures.An array of synthetic methods is used to synthesize mesoporous nanomaterials such as SiOThe hard-templating method, also known as nano-casting, uses a solid template material to create the mesoporous structure. The template is then removed to leave behind mesopores inside the material. The templates include preformed nanoparticles, carbon, or mesoporous silica. One of the advantages of this technique is that there is less of a need to control the hydrolysis and condensation to help them favorably interact with the templates, which need to be considered when carrying out soft template-assisted co-condensation or self-assembly methods . One of The soft-templating method uses soft matter or self-assembling substances that can serve as templates to produce the mesoporous structures in the materials. This method, for example, involves co-assembling surfactant molecules, such as Pluronic-123 and silicate guest species, to form an ordered mesoporous silica structure. This process can be performed in aqueous and nonaqueous solutions  processes, respectively) . The temWhile titania and carbon materials have been studied for the removal of emergent pollutants, including drugs with a rising prevalence in water systems , the num2-activated porous carbon that was derived from stevia residue for the adsorption of TCS [2 g−1 and an adsorption capacity of 117 mg g−1 for TCS. Furthermore, their work indicated that the ability of the material to adsorb TCS varied with the pH of the solution as well as the surface area of the material. Because of its high adsorption capacity and the inexpensiveness of its precursor, CO2-activated porous carbon is a promising alternative material for the removal of TCS from solutions.Generally, two approaches have been considered to remove these phenolic compounds or their derivatives from water by using mesoporous nanomaterials: adsorption and photocatalysis. In terms of adsorption-based extraction of TCS and other phenolic compounds from solutions, carbon materials have been widely studied. They were also among the first materials to be explored for this purpose. Carbon materials possessing good adsorption capacity for TCS can be made by designing their structures well enough to be able to adsorb this compound efffectively. For example, Yokoyama et al. investigated the ability of COn of TCS . Their tAn excellent overview of the details of adsorption kinetics for contaminants in aquatic systems, along with the rate-limiting variables associated with the processes, is reported by Tan et al. . Readers2 nanoparticles could be described with a first-order kinetic model [There have been differing views about the order of kinetic models involved in the adsorption of compounds on various adsorbents though. While numerous environmental studies have adopted pseudo-second-order models for adsorption processes involving pollutants such as TCS ,54,55, oic model . Neverthic model . Unfortuic model ,58,59. Aic model , a situaOne of the main challenges with the photodegradation of TCS is the formation of intermediates that can be more harmful in aquatic systems than TCS itself. For example, during photolysis, TCS can become 2,8-dichloro-dibenzo-p-dioxin, a carcinogenic substance ,61. In t−) is present at pH > 7.8. The effects of pH on TCS’s ionization as well as degradation pathways in solutions under different conditions have been studied by various groups. For example, Solá-Gutiérrez et al. reported that the anionic form of TCS (pH > pKa: 7.9–8.1) would absorb light more readily than its neutral counterpart [TCS is an ionizable compound, with pKa = 7.8, that can exist in two different forms in solutions depending on the pH of the solution. The neutral form (which is often referred to as HTric) exists mainly at pH < 7.8, while the anionic form  as reactive oxygen species (ROS), rather than the •OH species that had been proposed in multiple photodegradation pathways in many other systems [2−x nanomaterials that can serve as highly effective and stable photocatalysts and that can operate both under UV and visible light have recently been developed by our group and others [Given that the pH in waste streams can vary, it is therefore also essential to design alternative mitigation methods that enable TCS to undergo the right course of photodegradation processes in solutions with different pH values. One such method involves the incorporation of photosensitizers that can help the photocatalytic conversion of TCS into harmless intermediates or products, as demonstrated by Marazuela et al. . The aut systems ,65. It i systems . Thus, s systems ; thus, td others ,68. SuchThe photodegradation of TCS can be hindered by various competing species in solution. For example, if present in solution, 2-propanol inhibits the photodegradation of TCS ,70. ThisHybrid nanomaterials, which are comprised of two or more components, have been reported to have numerous applications, including in photocatalysis and environmental remediation/protection ,73,74,752 are suitable platforms to deposit other species on and thereby create such hybrid materials for photocatalysis applications [2 is limited to the ultraviolet region of light (λ ≤ 390 nm) because it cannot absorb the visible and infrared regions of sunlight—the most readily available sources of energy from the Sun—to photocatalyze reactions. Furthermore, its synthesis is complicated by the fact that the rapid hydrolysis and condensation of its precursors often result in non-porous materials with poorly defined structures, low surface areas, and low density of catalytically active sites. Therefore, finding alternative synthetic methods [Hybrid nanomaterials can be created by various synthetic techniques using different materials as platforms or by systematically mixing different components. Owing to their low cost and environmental friendliness, titania-based materials such as commercially available P25 TiOications . However methods  or alter methods ,79,80 th2–SiO2 can remove, via both adsorption and photocatalysis, the antibiotic tetracycline  more effectively than can pure TiO2 [2–SiO2) for this phenolic compound at a given pH was higher than that of TiO2. This is mainly because the hybrid materials have higher surface areas as well as more homogeneously dispersed TiO2 nanocrystallites than does pure TiO2. For instance, the hybrid material composed of 28 wt.% TiO2–SiO2 could photodegrade 60 µM of tetracycline in aqueous solution with 60% higher performance than the same amount of bare TiO2 could do. Thuis, such hybrid materials can serve as excellent platforms for both adsorption and photocatalytic degradation of tetracycline.To this end, Brigante et al., for example, showed that hybrid mesoporous materials composed of TiOure TiO2 . FurtherThe incorporation of silica, especially in nanostructured and nanoporous form, into photocatalytic active materials is also proven to improve their applications in photocatalysis rendering the hybrid materials effective photocatalyts for the remediation of environmental pollutants. The nanostructured/nanoporous silica makes this possible by helping create large surface areas and controlled/tunable nanopore sizes in the hybrid materials . For exa2 nanomaterials was found to photodegrade organic dyes more selectively than commercial P25 TiO2 (Degussa) does, even if the former exhibited less adsorption capacity than their solid counterparts [2 (TiO2/SBA-16) to exhibit photocatalytic activity for degradation of phenol than pure TiO2 [2 (Degussa) photodegraded only 27% of phenol in solution in 5 h, 10% TiO2/SBA-16 enabled the removal of 62% phenol in solution in the same period under the same experimental conditions. While in this work, phenol was studied as a model pollutant, it could serve as a framework for exploring the potential photocatalytic application of such materials for the degradation of TCS and other common phenolic emerging pollutants in the same way [The structures of the materials can also affect how selective as well as how effective the photocatalytic properties of the hybrid materials will be towards specific pollutants. For example, hollow TiOterparts . In anoture TiO2 . While asame way . More imFunctionalizing the surfaces of nanoporous materials with different moieties can improve the ability of the materials to adsorb and remove pollutants such as TCS from aqueous solutions. For example, Toufaily et al. synthesized organic-functionalized SBA-15 mesoporous silica using organosilanes that contain thiol and amine groups to improve the material’s selectivity to adsorb and extract phenolic compounds from aqueous systems . The adsIncorporating monometallic nanoparticles and bimetallic nanoalloys into nanoporous support materials, e.g., semiconducting metal oxides, is another promising strategy for producing nanostructured photocatalysts for emerging pollutants. The nanoparticles can constitute favorable electronic and structural properties and synergistic effects that enable effective photocatalysis. Noble metal nanoparticles can do so, for example, by absorbing light via surface plasmonic resonance (SPR) or by stabilizing the charge carriers (electrons and holes) forming on the semiconducting metal oxides upon light illumination. Additionally, metal nanoparticles can serve as electron traps, thereby reducing the recombination of the charge carriers on semiconducting metal oxides and improving their chances to transfer to adsorbates to degrade them. Furthermore, the immobilization of metals on the surfaces of other materials can create photocatalytic groups that enable the decomposition of adsorbates/pollutants . The imm2 and then investigated the effects of the metals on the materials’ photocatalytic performances under UV and near UV-Vis light irradiation using phenol as a model pollutant [2, 0.5% Cu-doped TiO2 was found to degrade phenol faster than commercial P25 TiO2 catalyst in the first 30 min. However, the metal-doped TiO2 could not fully degrade phenol in the UV-Vis region. Interestingly though, all synthesized metal-impregnated photocatalysts showed more efficient and faster kinetics in removing phenol in the near UV-visible region compared to P25-TiO2. Their photocatalytic activities were different from each other though. The sizes of the crystallites and the surface area of the materials were ruled out from being the main factors in the differences in the activity of these photocatalytic materials since the sizes of the particles in the three catalysts were comparable. A relevant factor was proposed to be the fact that metal dopants act as hole (h+)- and/or electron (e−)-trapping sites, which, in turn, impede the rate of electron/hole pair recombination, thereby increasing the ability of the charge carriers to participate in the redox processes during photocatalysis.To this end, various metallic nanomaterials have been integrated with photocatalytically active systems to improve the performances of the photocatalysts. For instance, Belekbir et al. incorporated/doped different amounts of different metals  into nanosized TiOollutant . In the 3N4, rendering the hybrid material photocatalytic active toward environmentally relevant reactions. Of note, they showed that the material enables photocatalytic oxidation of phenol and hexavalent chromium (Cr(VI)), another ubiquitous pollutant, individually as well in tandem (3N4 (denoted CNM-AP) in comparison to the one catalyzedt by Au-modified or Pd-modified MCM-41/g-C3N4 . However, the rates of removal of phenol via oxidation over the materials decreases as the concentration of Cr(VI) increases  species [As mentioned previously, the presence of phenolic intermediates must be accounted for when designing photocatalytic systems since the intermediates themselves can also exhibit toxicity. Thus, photocatalytic systems that drive the total oxidation of the organic pollutants are more desirable. For the system discussed above, for example, the intermediate aromatic compounds were oxidized further via a ring-opening reaction into CO species . Another species ,92,93.2@TiO2 microspheres and then demonstrated their photocatalytic properties under visible light for the degradation of phenol [2) under the same conditions. The nanomaterials were synthesized by anchoring Ag and Cu alloy nanoparticles onto SiO2@TiO2 core-shell microspheres through multistep synthetic processes involving sol-gel and chemical reduction methods. The authors also tested the photocatalytic properties of the materials synthesized with different ratios of Cu/Ag  resulted in a higher reaction rate for the degradation of phenol than those containing other ratios of Ag-to-Cu. The degradation of phenol via oxidation on these materials is attributed to the participation of hot holes generated by the bimetallic nanoalloys and the holes generated on TiO2. These holes participate in the reaction better and enhance the material’s photocatalytic activity because the energy barrier formed at the metal alloys/TiO2 interface suppresses the electron-hole recombination, leaving most of the holes available for the degradation reaction.In another interesting recent work, Babu and Naik synthesized Cu and Ag bimetallic nanoalloys-decorated SiOf phenol . They alof Cu/Ag . Their rIt is worth adding here that the photocatalytic processes involving TCS and other related phenolic compounds over various metal oxides could also be inhibited by various unwanted processes. Although the metal oxide particles help produce ROS that promote the photodegradation of TCS in suspensions, they could prevent light from reaching all the reactive sites on the materials. This could, in turn, reduce the photodegradation of TCS and other phenolic compounds over the materials. Furthermore, the photodegradation of TCS and the other phenolic compounds by metal oxides could produce secondary pollutants in the environment by forming other toxic intermediates or byproducts, as illustrated in Another aspect to consider when designing photocatalysts for the degradation of emerging phenolic compounds is to have them perform additional functions. This means a photocatalyst used for the degradation of phenol and related species can be designed to have also antibacterial, antifouling, or anticorrosive properties for environmental protection. Several research groups have recently ventured into this area and obtained promising results. 2 photocatalyst co-doped with cobalt and nitrogen for the degradation of TCS [Legionella pneumophila, a common pathogen found in aquatic environments. These two properties that this material exhibits can make this material suitable for water treatment where both TCS or other phenolic species and pathogens are present.For example, Ferreira et al. synthesized a visible-light-driven TiOn of TCS . An inten of TCS . NotablyIn a complementary line of work, Coelho et al. developed a photocatalytically active zirconia-titania ultrafiltration membrane that can photodegrade phenol and humic acid under simulated sunlight irradiation . As a se2 and carbon (C) materials to degrade phenol via photothermal-assisted triphase photocatalysis [Huang et al. developed a bilayer catalytically active paper composed of TiOatalysis . Their w2, TiO2, or both are considered and included in the table. Note that these materials are doped with other elements to bring about (good) photocatalytic activities or other desirable secondary functionality. These materials are chosen among many others for illustrative purposes.TCS and other phenolic compounds and their derivatives are becoming ubiquitous in the environment, especially in aquatic systems, and are causing a significant impact there due to their wide applications in various consumer products. While there have recently been increased reports in the literature on their potential negative side effects, more research is necessary to find ways to remove these emerging pollutants from the environment. It is also important to understand the adsorption kinetics and mechanisms involving such emerging pollutants in various systems in order to design and fabricate materials that can helo with the removal of these compounds from the environment. Equally important, new materials to effectively capture remove, and decontaminate these pollutants, even before finding their way into aquatic systems and water systems, must be developed. In this review, the unique properties, structures, and compositions of silica- and titania-based nanomaterials being developed for the removal and photocatalytic decontamination of TCS and other phenolic compounds from the environment are discussed. While several materials have been considered and explored for these purposes, mesoporous silica and titania are among the most notable ones. These two materials are viable platforms for the adsorption of these compounds from the environment because of their robust structures, recyclability, and potential for anchoring other functional groups to increase their adsorption affinity for these compounds. In addition, their pore sizes and structures can be tuned to tailor their adsorption capacity for these pollutants as well as to study the adsorption kinetics between the pollutants and the materials. Some of them can also photocatalyze the decontamination of TCS and various other phenolic compounds and enable the studies of the photocatalytic processes and mechanisms associated with these emerging environmental pollutants. Some of the works performed in this area include the development of various photocatalytic materials for the degradation of these compounds. One commonly applied process involves the conversion of TCS and phenolic compounds to harmless byproducts using a catalytic or photocatalytic component incorporated within the pores of the mesoporous materials. However, further research into the development of highly active, selective, and recyclable nanostructured photocatalysts able to perform such conversions is still currently needed.Most recently, there has also been a push to develop multifunctional materials that can degrade TCS and other phenolic pollutants in the environment via photocatalysis as well as that can address other problems typically associated with water remediation operations such as fouling, bacterial contamination, or persistent organic pollutants. Since such materials can potentially perform multiple functions at the same time, they are of greater interest for applications in the decontamination of water systems.There have been advances in the stability and recyclability of these materials, but additional research is needed to scale up and deploy them in existing operations. Other aspects to consider are the logistics and potential for recovering and reusing these materials once the adsorption and photocatalytic processes are carried out. These issues should be addressed before any industrial-scale implementation of these various nanomaterials is developed for decontamination of the environment from TCS and other ubiquitous phenolic compounds.


Here, we identify a significant seasonal advance of intense TCs since the 1980s in most tropical oceans, with earlier-shifting rates of 3.7 and 3.2 days per decade for the Northern and Southern Hemispheres, respectively. This seasonal advance of intense TCs is closely related to the seasonal advance of rapid intensification events, favoured by the observed earlier onset of favourable oceanic conditions. Using simulations from multiple global climate models, large ensembles and individual forcing experiments, the earlier onset of favourable oceanic conditions is detectable and primarily driven by greenhouse gas forcing. The seasonal advance of intense TCs will increase the likelihood of intersecting with other extreme rainfall events, which usually peak in summer7, thereby leading to disproportionate impacts.Intense tropical cyclones (TCs), which often peak in autumn We identify a seasonal advance of intense tropical cyclones that is closely related to the seasonal advance of rapid intensification events, favoured by the observed earlier onset of favourable oceanic conditions. Global warming caused by human activities is estimated to be about 1.0 °C above pre-industrial levels, with most of the warming occurring since the mid twentieth century10. This warming may have already impacted TC activity on the global scale13. Although changes in the annual number of global TCs are controversial14, an increasing trend in the number of global intense TCs has been noted14, and significant efforts have been devoted to reducing uncertainties in data quality issues16. Poleward migration of the locations of TC activity was observed in most ocean basins in recent decades and is particularly robust in the western North Pacific basin19, which is related to changes in TC seasonality20. A recent study21 identified an earlier onset of the beginning time of TC season, in terms of the initial formation dates, in the North Atlantic basin associated with a warming ocean in spring, but there is no seasonal change in the date that Atlantic accumulated cyclone energy reaches its 10, 50 or 90% threshold. Overall, detection and attribution of changes in TC activity are among the top priorities of TC research22.Tropical cyclones (TCs) are one of the most devastating natural disasters in the world. Understanding potential changes in TC activity in response to global warming is important for TC-related disaster prevention24. Most regions lack resilience to intense TCs, which could cause many deaths and damage to property through destructive winds, storm surges, heavy precipitation and inland flooding27. For these reasons, it is crucial to understand changes in intense TC characteristics29. Although it is still challenging for high-resolution climate models to capture intense TCs31, statistical analysis suggests that intense TCs are likely to be more susceptible to anthropogenic warming compared with other TC categories32. Changes in many characteristics of intense TCs under a warming climate  are fairly well studied; however, little is known about changes in the seasonal cycle of intense TCs.Intense TCs (TCs with a lifetime maximum wind speed greater than 110 kt) that pose the greatest threat require special attention2. The seasonal cycle of intense TCs lags behind that of other high-impact weather events , which often peak in summer and are largely determined by the seasonal cycle of atmospheric energy driven by solar radiation7. Recently, the compound hazards of intense TCs and other high-impact weather events have attracted increasing attention34. The devastating impact of the compound hazards is well beyond any one of these events individually. They can induce substantial inland rain and flooding associated with multiple weather systems, causing large-scale failures of power and transportation systems, straining emergency responses and depleting disaster preparation resources5. As the preferred time of occurrence of intense TCs and other high-impact weather events is usually off by one season, the likelihood of their simultaneous occurrence is generally assumed to be small; however, given the seasonal advance of intense TCs, as shown in this study, its potential change should be considered.In general, intense TCs occur more frequently in autumn than in summer because they require sufficient heat from the ocean to developWe begin with a broad view of the change in the seasonal cycle of intense TC occurrence. The occurrence time of an intense TC is defined by the date on which the TC first achieves its lifetime maximum intensity. TC data during 1981–2017 are taken from the advanced Dvorak Technique–Hurricane Satellite (ADT-HURSAT) dataset (‘TC observations’). Figure 35 and the rarity of intense TC occurrence in the eastern part  in the number of intense TCs Fig. . The incThe time series of the median value of intense TC occurrence time during the active season in two hemispheres based on the ADT-HURSAT dataset are shown in Fig. To confirm whether the seasonal advance only occurs in the intense TCs, we quantify the shifting rates of TCs with different intensities. Using the ADT-HURSAT dataset and best-track dataset (‘TC observations’), the results consistently show a significant earlier-shifting trend for intense TCs in two hemispheres based on a non-parametric statistical test but not for less intense TC events Fig. . Note th36. In contrast to most other natural phenomena, the probability density function of the lifetime maximum intensity for all TCs is bimodal, with the first maximum around 50 kt and the second one around 120 kt. The existence of the second maximum indicates that there may be a special mechanism that causes a TC to intensify after its intensity exceeds a certain threshold, thus inducing more intense TCs than expected28. Ref. 36 found that the bimodal distribution of TC lifetime maximum intensity could be divided into two unimodal distributions when all TC events were classified into two groups according to whether they experienced an RI process or not. It was also found that the vast majority of intense TCs underwent the RI process at least once during their life cycles and that only a few TCs that never experienced the RI process would develop into intense TCs. It is thus clear that the RI process is the key that distinguishes intense TCs from other TCs. A natural question, therefore, is whether a similar earlier shift can be found for the seasonal cycle of RI events, which are defined as events with an increase of at least 35 kt over a 24 h period (approximately the 95th percentile of 24 h intensity changes) (‘RI events’).Intense TCs generally experience rapid intensification (RI) in their lifespanAs expected, a clear earlier shift in the seasonal cycle of RI events is observed 41 and ocean heat content (OHC) must be very high for RI to occur38. The former is the theoretical maximum intensity that a TC can achieve and is mainly moderated by sea surface temperature43. For the atmospheric part, high atmospheric relative humidity (RH) is beneficial for TC development44. The vertical wind shear (VWS) should not be excessively large; otherwise, the TC development process is suppressed45.To investigate the reason for the earlier shift in RI occurrence, we examine the seasonal cycles of the oceanic and atmospheric conditions  favourable for the RI of TCs45, the seasonal cycle of the atmospheric factors does not show a significant change based on three atmospheric reanalysis datasets  and fifth-generation global atmospheric reanalysis ERA-5) datasets Fig. . It is c datasetsAn earlier onset of favourable oceanic conditions is detectable in simulations from global climate models. Figure 44, which is caused by the weakened surface wind in summer46.Whether the detected earlier-shifting trend in favourable oceanic conditions is driven by anthropogenic or natural forcing remains unknown. To address this question, we compared the contributions of the greenhouse gases (GHGs), natural forcing and anthropogenic aerosol based on the Detection and Attribution Model Intercomparison Project (DAMIP) in CMIP6, which conducted the individual forcing simulations in the historical period (‘Model simulations’) experiments. Under GHG forcing Fig. , there i48, with the first peak (in June) influenced by the summer monsoon system and the second peak (in October) induced by TC landfall. An obvious increase in extreme rainfall events is observed during the gap period between the two peaks (July to September). This may be related to the pronounced earlier shift of intense TC occurrence over the western North Pacific basin  become more beneficial for the intense TCs in the early season than those in the late season, thus favoring the seasonal advance of the intense TCs. In contrast, the changes in the atmospheric factors are either modest or insignificant, and thus, they do not contribute much to this earlier-shifting trend. The earlier onset of favourable oceanic conditions is detectable based on both the multimodel mean of the CMIP6 historical simulations and the CESM2 large ensemble. To investigate whether the detected earlier-shifting trend in favourable oceanic conditions is driven by anthropogenic or natural forcings, we compared the contributions of the GHG, natural and anthropogenic aerosol forcings based on individual forcing experiments from the DAMIP  and that produced by intense TCs. This overlap could create devastating impacts that are well beyond any one of these events individually12 dataset provides globally homogenized TC records derived from satellite imagery during the period of 1981–2017. The ADT-HURSAT dataset is created with TC track data from the operational dataset and the TC intensity data estimated from global geostationary satellite imagery, which are homogenous in time and region. Global TC best-track data during the period of 1981–2021, obtained from the International Best Track Archive for Climate Stewardship v.4 (ref. 51), are exploited to further confirm the results based on the TC data derived from the ADT-HURSAT dataset. To analyse global trends, the ADT-HURSAT dataset is homogenized and used as a priority. There is some uncertainty in the absolute value estimates of TC intensity in the ADT-HURSAT dataset, and the best-track data are likely to have lower-intensity errors when looking at individual storms and seasons53. Consistent with the above findings obtained from the ADT-HURSAT dataset, the earlier-shifting trend of intense TC occurrence based on the best-track dataset is also statistically significant in both hemispheres  during their lifetime, are also considered.Special attention is paid to intense TCs. An intense TC means its lifetime maximum intensity is over 110 kt, which is equivalent to a category 4–5 TC based on the Saffir–Simpson scale51. Furthermore, measurements of TC intensity are often much more stable near the TC lifetime maximum intensity. Note that the TC season in the NH is defined as the current calendar year, whereas the TC season in the SH is defined from 1 July of the last calendar year to 30 June of the current calendar year as the seasonal distribution of TC activity in the SH straddles the calendar year.The occurrence time of an intense TC event is defined as the date on which it first achieves its lifetime maximum intensity. This is determined by the relative change in TC intensity rather than the absolute value, which ensures the reliability of resultsThe median value of intense TC occurrence dates during the active season is calculated. The active season is defined as June to November in the NH and December to April in the SH, comprising approximately 85% of all TC events. The early season is defined as the first half of the active season , and the late season is defined as the second half of the active season .54. The expected value (μ = α/(α + β)) of the occurrence date is calculated under the assumption that the seasonal cycle of intense TCs approximately follows a beta distribution, where α and β are beta parameters. This assumption is justified because the seasonal occurrence date of intense TCs is bounded on both ends. Beta distribution parameters are usually fit using the method of the moment. Results from the expected occurrence of intense TCs support the same conclusion  is used and defined as the integrated heat content from the sea surface down to the 26 °C isotherm55, Four environmental factors that may be related to the RI process are considered, including PI, OHC, RH and VWS. PI and OHC are referred to as oceanic factors, whereas RH and VWS are atmospheric factors. PI is the theoretical maximum intensity that a TC can achieve and is determined by sea surface temperature and the associated thermodynamic profile56 monthly Ocean Reanalysis database and the Global Ocean Data Assimilation System57. The atmospheric variables are obtained from the ERA-5 dataset58, Japanese global atmospheric 55-year reanalysis59 and Modern-Era Retrospective Analysis for Research and Applications v.2 (ref. 60). With improvements in assimilation schemes and numerical weather prediction models, the reanalysis reliability can vary considerably depending on the location and evaluation metrics61.The oceanic variables are obtained from the ECMWF43. Consistent with ref. 43, we found that stronger PI, higher OHC, higher RH and weaker VWS are all beneficial for RI. The exact value differs from that by Bhatia et al.43, as we use 35 kt as the threshold of RI definition rather than the 30 kt used by Bhatia et al.43. This result suggests that it is reasonable to use the high quartiles of PI, OHC and RH and the low quartiles of VWS to indicate the environmental conditions that lead to RI. Although the local conditions experienced by TCs should be more relevant for the likelihood that they undergo RI, it cannot be obtained with good accuracy in the low-resolution climate model simulations in which the TC and RI process cannot be represented well . Instead, the fractional area coverage by high-percentile PI and OHC, also corresponding well to RI events, is simple and can be directly calculated from the simulations. Here, the favourable conditions are quantified by the fractional area covered by high PI, high OHC, high RH and low VWS relative to the overall tropical ocean area . The area covered by high PI, high OHC and high RH is defined as the sum of the area with the corresponding value above its 95th percentile, respectively, whereas the area covered by low VWS is defined as the sum of the area with the VWS lower than its 5th percentile. A sensitivity analysis was conducted where the 90th percentile of PI, OHC and RH and the 10th percentile of VWS were used. Consistently, an earlier shift of the seasonal cycle favourable oceanic conditions is obvious  simulations during 2080–2099 of 20 models from CMIP6 are considered (Extended Data Table 63) is also used, by which internal variability could be largely suppressed.To detect the earlier-shifting trend of favourable oceanic conditions, we use the multimodel mean of environmental factors from phase 6 of the CMIP6 simulations65. Although the large-scale environmental fields are the focus of our study, it would be better to make a comparison of the results obtained from the high-resolution and low-resolution model outputs of CMIP6 HighResMIP simulations. The historical simulations  from these five pairs  of high-resolution and low-resolution models are used: CNRM-CM6-1-HR and CNRM-CM6-1; EC-Earth3P-HR and EC-Earth3P; ECMWF-IFS-HR and ECMWF-IFS-LR; HadGEM2-GC31-MM and HadGEM2-GC31-LL; and INM-CM5-H and INM-CM5-0. These model pairs contain all the variables needed. The HighResMIP multimodel ensemble analysis shows that the earlier onset of the high percentiles of PI and OHC is evident based on both the high-resolution and the low-resolution model outputs  are prescribed; and hist-aer, in which only anthropogenic aerosols are prescribed. In total, these nine models with all the outputs needed are used: ACCESS-CM2, BCC-CSM2-MR, CanESM5, CESM2, FGOALS-g3, GISS-E2-1-G, IPSL-CM6A-LR, MRI-ESM2-0 and NorESM2-LM. For each model, only one realization is used in each experiment.To address whether the earlier onset of intense TCs is anthropogenic or natural forcing, all available experiments from the DAMIP67. The extreme rainfall events are counted in South China  and the Gulf of Mexico .The occurrence frequency of an extreme rainfall event is defined as the number of days with a rainfall amount over 50 mm, which is approximately equivalent to the 95th percentile of the daily rainfall. The rainfall data are obtained from the Climate Prediction Center Global Unified Gauge-Based Analysis of Daily Precipitation dataset69.The extreme rainfall events induced by intense TCs are calculated as a rainfall amount over 50 mm over intense TC-centred circles with a radius of 500 km. The radii of 500 km were chosen based on previous analyses of TC rainfall70. Following a simple definition of the persistent rainfall event proposed by ref. 69, the absolute threshold of daily precipitation amount exceeding 50 mm for at least three consecutive days is used. Note that a more elaborate analysis of the compound hazard of intense TCs and other high-impact events requires a careful definition of the compound hazard and quantitative examination of its change, which will be addressed in a future study.In addition, the persistent rainfall event is used as an example of compound hazards, which occur during the overlap period between extreme rainfall produced by other weather systems  and that produced by intense TCs. A persistent rainfall event can lead to disproportionate impacts by inducing a superimposed elevation of water levels and a shortage of disaster preparation resources72. The Student’s t-test is used to evaluate the 95% confidence intervals of the linear trend estimate74. The uncertainty of the multimodel mean is represented by the s.d. (ref. 75).The Mann–Kendall test is employed to determine if a statistically significant trend at a special level is achieved. This approach is non-parametric, so knowing the distribution for the data series is not required. This property enables the Mann–Kendall test to be applicable to the number of TC events or other extreme events in particularAny methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41586-023-06544-0.Peer Review File


The value of birds’ ability to move the upper beak relative to the braincase has been shown in vital tasks like feeding and singing. In woodpeckers, such cranial kinesis has been thought to hinder pecking as delivering forceful blows calls for a head functioning as a rigid unit. Here, we tested whether cranial kinesis is constrained in woodpeckers by comparing upper beak rotation during their daily activities such as food handling, calling and gaping with those from closely related species that also have a largely insectivorous diet but do not peck at wood. Both woodpeckers and non-woodpecker insectivores displayed upper beak rotations of up to 8 degrees. However, the direction of upper beak rotation differed significantly between the two groups, with woodpeckers displaying primarily depressions and non-woodpeckers displaying elevations. The divergent upper beak rotation of woodpeckers may be caused either by anatomical modifications to the craniofacial hinge that reduce elevation, by the caudal orientation of the mandible depressor muscle forcing beak depressions, or by both. Our results suggest that pecking does not result in plain rigidification at the upper beak's basis of woodpeckers, but it nevertheless significantly influences the way cranial kinesis is manifested. It coWhile the adaptive advantage over akinetic skulls (i.e. skulls with a fixed upper beak) is not always clear, selective forces promoting cranial kinesis strongly depend on the ecological context . Roles os.l.), but became secondarily reduced in the most derived clade, the Malarpicini [Cranial kinesis of woodpeckers (Picidae) is hypothesized to be selected against because of its counterproductive effect on forceful pecking ,17. Accoarpicini . During arpicini . This searpicini .Here, we tested the hypothesis that pecking is linked with an overall constrained cranial kinesis (i.e. magnitude of either upper beak elevation or depression), and with a restricted upper beak elevation in particular , by comp. 2 (a)α between three landmarks (a) was measured on each image using TpsDig software [β was estimated using the abovementioned landmarks (1) and (2), and (3) the lower beak tip (a). To allow subpixel coordinate digitizations, the pixel resolution of the images was increased by 2.5 times in both height and width using Adobe Photoshop . Upper and lower beak rotations were calculated by subtracting the closed-beak α or β from, respectively, the α or β at maximum gape. Our angle definition (a) implies that positive values denote beak elevations with respect to the cranium. The total amount of cranial kinesis irrespective of the direction of the rotation was obtained by taking the absolute value of upper beak rotation. To account for error in landmark placement, angle measurements were repeated three times and the averages were used in the analyses.About 10 000 video clips from the Macaulay Library of wildlife recordings of Cornell University  were scrandmarks a was measoftware : (1) thebeak tip a. To allfinition a impliesc. Osteological nomenclature was taken from Baumel et al. [Beak rotations were measured from 39 video clips of woodpeckers  and from 41 videos of other families of insectivorous birds from their two most closely related orders (i.e. Coraciiformes and Passeriformes ) and frofigure 1l et al. . (b)t-test) and phylogenetic statistics. Parametric t-tests were possible since data distributions for upper beak angles did not differ from normality in the groups (Shapiro–Wilk test), and no significant differences in variance were found (two-sample F-test for variance). Phylogenetic analyses were run on the complete Bayesian maximum clade credibility species-level avian phylogeny [D-test for binary traits [Differences in upper beak rotation between pecking and non-pecking species were assessed using traditional (hylogeny  pruned thylogeny ) tested y traits . Lastly,. 3Jynx torquilla; singing/calling) to elevations of 2.63  . Depressions of the upper beak during lowering of the mandible were observed in 13 of the 14 woodpecker genera studied. In our sample of other insectivore birds, the upper beak rotated between −4.1 degrees  and 7.97 degrees  with respect to the cranium . Among the non-woodpecker insectivores, birds from three coraciiform families  showed depression of the upper beak, representing 15% of the species analysed. Neither Passeriformes nor the other families of Coraciiformes and non-pecking Piciformes analysed presented depression of the upper beak. In Schoeniophylax phryganophilus (Furnariidae), the elevation of the upper beak without movement of the lower beak was observed (6.25 degrees of upper beak rotation), but in the same video  also a beak opening was observed with depression of the mandible showing virtually no movement (−0.18 degrees rotation) of the upper beak.When pooling the measurements from different behaviours, upper beak rotations in woodpeckers ranged from depressions of −7.91 degrees (b). The slope of upper versus lower beak rotation showed an opposite relationship in woodpeckers compared with the other insectivore birds: increasing lower beak depressions were related to increasing depressions of the upper beak in woodpeckers , and to increasing elevations of the upper beak in the other insectivore birds  (b).Increasing cranial kinesis was observed for increasing lower beak depressions b. The sl= −0.29) b.t = −6.77, d.f. = 68, p < 0.001, two-tailed) (c). Similar differences were present in upper beak rotation during singing or calling, with respectively −4.3 ± 1.6 and 0.36 ± 2.29 degrees . The same trend in upper beak rotations was observed within food handling and gaping, but no statistical tests were possible owing to the limited number of samples for these behaviours (c). Cases with limited cranial kinesis (less than 1 degree) appeared less frequent in woodpeckers (12.8%) than in the other insectivores (35.7%) when considering all behaviours pooled together (d). The mean and median values of cranial kinesis were higher in woodpeckers (2.51 and 2.8 degrees) than in the other insectivore birds (1.48 and 0.74 degrees) (d).Mean upper beak rotations in woodpeckers and other insectivore birds were, respectively, −2.7 ± 2.1 degrees and 1.3 ± 2.7 degrees (mean ± s.d.), and differed significantly between two groups (-tailed) c. Similahaviours c. Cases together d. The medegrees) d.F = 45.8; p = 0.198) (e). This result was expected because woodpecking displays an extremely clumped phylogenetic pattern  as the trait evolved only once in the woodpecker lineage of Picidae (e).Contrary to traditional statistics, phylogenetically informed statistics did not reveal a significant difference in upper beak rotation between woodpeckers and non-woodpecking insectivore birds (= 0.198) e. This r Picidae e.. 4d). However, the hypothesis that elevation of the upper beak is generally restricted in woodpeckers was confirmed. A depression of the upper beak in woodpeckers was generally observed, while in closely related insectivores the upper beak typically is elevated . Although phylogenetically informed statistics could not prove that this pattern of upper beak movement is an adaptation to pecking at wood in the analysed taxa, the power of this test was inevitably limited owing to the woodpeckers’ monophyly (e). In line with previous measurements of beak kinematics during beak retraction after pecking [b–d). Further work may test whether the variation in the upper beak's range of motion between species can be linked to the morphology of the nasofrontal joint, such as the frontal overhang.Our findings do not support the hypothesis that overall cranial kinesis (regardless of upper beak rotation direction) is reduced in woodpeckers as a likely adaptation to forceful pecking d. Howeveelevated b,c,e. Alonophyly e. In lin pecking , upper bsensu [As the abovementioned frontal overhang could restrict elevation but will not generate upper beak depressions, what explains this movement in woodpeckers? The line of action of the m. depressor mandibulae may play a role . Previousensu ), onto wb), despite their generally having the postorbital ligament [Scolopax [Rhynchops niger [Columba livia [S. phryganophilus). This movement may thus be more common than originally thought. Together, these findings suggest that birds have an elaborate control of upper beak movement by the musculature of the quadrates and pterygoid bones. This is in line with several studies showing that a stringent role of the postorbital ligament in upper beak elevation coupled to mandible depression is often absent [Our data show that coupled kinesis where the maxilla elevates as the mandible depresses is generally absent in woodpeckers b, despitligament , which hligament . Also foScolopax  and the ps niger , and forba livia . Our mean absent ,10,35.In conclusion, our study showed that cranial kinesis is not reduced in woodpeckers, but instead shifted predominantly towards depressions instead of elevations of the upper beak. This may be linked to presumed morphological adaptions to pecking, such as a frontal overhang, resisting strong upper beak elevation as hypothesized earlier . We pred


Mucormycosis is a rare but life-threatening fungal infection due to molds of the order Mucorales. The incidence has been increasing over recent decades. Worldwide, pulmonary mucormycosis (PM) presents in the lungs, which are the third main location for the infection after the rhino-orbito-cerebral (ROC) areas and the skin. The main risk factors for PM include hematological malignancies and solid organ transplantation, whereas ROC infections classically are classically favored by diabetes mellitus. The differences between the ROC and pulmonary locations are possibly explained by the activation of different mammalian receptors—GRP78 in nasal epithelial cells and integrin β1 in alveolar epithelial cells—in response to Mucorales. Alveolar macrophages and neutrophils play a key role in the host defense against Mucorales. The diagnosis of PM relies on CT scans, cultures, PCR tests, and histology. The reversed halo sign is an early, but very suggestive, sign of PM in neutropenic patients. Recently, the serum PCR test showed a very encouraging performance for the diagnosis and follow-up of mucormycosis. Liposomal amphotericin B is the drug of choice for first-line therapy, together with correction of underlying disease and surgery when feasible. After a stable or partial response, the step-down treatment includes oral isavuconazole or posaconazole delayed release tablets until a complete response is achieved. Secondary prophylaxis should be discussed when there is any risk of relapse, such as the persistence of neutropenia or the prolonged use of high-dose immunosuppressive therapy. Despite these novelties, the mortality rate from PM remains higher than 50%. Therefore, future research must define the place for combination therapy and adjunctive treatments, while the development of new treatments is necessary. Mucormycosis is a rare but life-threatening invasive fungal infection caused by filamentous fungi of the order Mucorales. The incidence of mucormycosis has increased from 0.07 to 0.12 per 100,000 population during 2001–2010 in France; currently mucormycosis is the fourth most common cause of invasive fungal disease after fungemia, pneumocystosis and invasive aspergillosis ,4,5,6. AThe incidence is more pronounced in India, where it is nearly 70 times higher than in the rest of the world. The incidence in India increased from 1990 to 2015 . Rhino-oThe increased incidence over the last decades and the emergence of CAM, which has been widely reported in the media as “the black fungus threat” in India, brought mucormycosis to the attention of the public and health authorities. In the present narrative review on PM, we discuss recent updates on risk factors, physiopathology, diagnosis, and treatment.Pulmonary mucormycosis (PM) mainly occurs in immunocompromised patients . HematolThe main risk factor for PM is HM. Three studies conducted in North America, Europe, and France showed that among patients with PM, the proportion of patients with HM was high, from 50 to 80% ,15,16. ISolid organ transplantation (SOT) is the second most common risk factor for PM. Most PM cases occur during the first year post-transplant . In the COVID-19 now appears to be a risk factor for mucormycosis in patients with DM, especially in India. Uncontrolled DM and the use of dexamethasone, recommended in the treatment of COVID-19 requiring oxygen, were major additional risk factors for CAM ,21. InteDM and ketoacidosis are important risk factors, notably for ROC disease. The prevalence of DM-related mucormycosis has geographical variations. DM was more often reported in Asian (46%) and African countries (75%) compared to Western countries (36%) . In the Cases of PM have recently been reported in 21 patients who had pulmonary tuberculosis, representing five percent of the 388 cases of this cohort of mucormycosis .Syncephalastrum after hurricanes Katrina and Rita in 2005 in the USA [Trauma is another risk factor, mainly for cutaneous mucormycosis . A few p the USA .Healthcare-associated mucormycosis is rarely associated with primary lung involvement, but mainly with skin locations. In a review of the literature, PM accounts for six percent of health-care associated mucormycosis cases with an identified or suspected source of infection . Lung trBreakthrough mucormycosis has been frequently reported with voriconazole, which has no anti-Mucorales effects. This treatment appeared as an independent risk-factor for mucormycosis in case-controlled studies of HM patients ,35,36. WFew data are available regarding pediatric populations ,38,39. IWhat should be remembered? HM and SOT are the main risk factors for PM, whereas DM increases the susceptibility to ROC mucormycosis. A peak of COVID-19 associated mucormycosis occurred in May 2021 in India, involving mainly ROC forms.Mucorales spores are ubiquitous in nature, found in the soil and in decaying organic matter. Spores are airborne, leading to ROC, mostly in diabetic patients or to pulmonary form upon their inhalation in patients with HM or SOT. For a long time, the question was why there was such a difference in tissue targets. This difference has recently been explained, at least in part, by the activation of various mammalian receptors depending on the host cell type as nicely evidenced through the contribution of a UCLA group .Rhizopus arrhizus in endothelial cells in diabetic mice [First, the glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone protein of the HSP70 family, induced notably by an elevated level of glucose, has been identified as the host receptor for tic mice . Fungal tic mice .Afterwards, it was shown that the fungal CotH3 protein interacts with GRP78 on nasal epithelial cells as well  Figure . ElevateOn the other hand, fungal CotH7 recognizes integrin β1 as the receptor on alveolar epithelial cells. Integrins are highly expressed in human lung tissues. This binding triggers the activation of epidermal growth factor receptor (EGFR) signaling, leading to host cell invasion and pulmonary infection . InteresRhizopus by iron starvation [Drosophila model, corticosteroids, increased iron supply, and iron availability increased the pathogenicity of mucormycosis, as in humans [Alveolar macrophages have a predominant role in the host defense against Mucorales, through the control of spore proliferation, as demonstrated by Andrianaki et al. . First, arvation . This nuarvation ,46,47. Harvation ,49,50. Aarvation . In the n humans .R. arrhizus than A. fumigatus less efficiently. Differences have also been noted between the species of Mucorales. Interestingly, the production of oxidative burst is lower in response to the Rhizopus species compared to that recorded with Lichtheimia corymbifera [The importance of neutrophils is first shown by the fact that neutropenia is a major risk factor for mucormycosis. Neutrophils recognize Mucorales mainly by TLR2, leading to the production of pro-inflammatory cytokines ,53. Thesymbifera .Mucor irregularis infection [The development of mucormycosis in chronic granulomatous diseases (CGD) reinforces the understanding of the role of neutrophils in the defense against Mucorales. The mutation in the genes encoding the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, responsible for CGD, impairs the production of reactive oxygen species by neutrophils. Few cases or small case-series have reported mucormycosis ,60,61,62nfection .What should be remembered? Alveolar macrophages and neutrophils are major innate immune cells involved in the defense against Mucorales. The differences between ROC and pulmonary locations are explained at least in part by the activation of different mammalian receptors, GRP78 in nasal epithelial cells and integrin β1 in alveolar epithelial cells, in response to Mucorales invasion.PM is the third most common site of infection (20%), after ROC (34%) and cutaneous (22%) mucormycosis in a review of 600 published articles in the literature .Symptoms of PM are non-specific. Persistent fever despite broad spectrum antibiotics and pulmonary symptoms are suggestive of a pulmonary fungal invasive infection in a patient at risk . These sPM can have endobronchial involvement. Among 35 patients with HM and PM who underwent fiberoptic bronchoscopy, 34 had visible endobronchial diseases. The main findings were stenosis (24%), erythematous mucosa (18%), obstruction of airway (12%), gelatinous or mucoid secretions  . EndobroChest computerized tomography (CT)-scan is recommended in patients with a suspicion of pulmonary fungal infection. The presence of a reversed halo sign (RHS) is highly suggestive of PM ,72. It iOther findings are consolidation, nodules, halo sign, micronodules, mass, cavitation, and pleural effusion, but these are non-specific. In the recent retrospective French study on PM, condensation and ground glass opacities were the predominant lesions  . NeutropOne of the difficulties is to find radiologic features suggesting PM rather than pulmonary aspergillosis as they share the same risk factors and clinical presentation but may not require the same treatments. The presence of more than 10 nodules  and of pleural effusion  were predictors of PM compared to pulmonary aspergillosis in a retrospective study of patients with cancer . AnotherIn patients with suspected or confirmed PM, other locations should be systematically investigated. Sinus involvement is frequently reported in patients with PM; the reported frequencies varied from 13% to 95% of the cases ,68,78. T18F-Fluorodeoxyglucose positron emission tomography CT (PET/CT) has shown interesting results in small series for the diagnosis, the staging and the treatment’s duration ,84,85. PWhat should be remembered? A reversed halo sign is an early and transient, but very suggestive, sign of PM in neutropenic patients. Other locations of mucormycosis should be evaluated with a body CT-scan and cerebral imaging.Rhizopus, Mucor and Lichtheimia, followed by Apophysomyces, Cunninghamella, Rhizomucor, and Saksenaea [Rhizomucor, Rhizopus, and Lichtheimia were predominantly identified in 32%, 30%, and 25%, respectively [Cunninghamella were more common in patients with PM or with disseminated forms, whereas that of Rhizopus was more frequent in ROC mucormycosis [Saksenaea and Apophysomyces were mostly associated with cutaneous mucormycosis, but not PM. There are also geographical variations: Lichtheimia species were predominantly documented in Europe, whereas Apophysomyces species were not observed in Europe or Africa.The three most frequent human pathogens in mucormycosis are the species of aksenaea ,82. In tectively . Speciesrmycosis . SaksenaAspergillus coinfection [The diagnosis of mucormycosis is made harder to establish by the existence of mixed mold infections. In a series of 690 patients with invasive aspergillosis, 25 of them (4%) had concomitant mucormycosis . Among tnfection .3 [Mucorales are identified by culture and non-culture methods from specimens, such as tissue biopsy, broncho-alveolar lavage (BAL) fluid or other respiratory samples, and serum. Every effort should be made to obtain specimens. For PM, bronchial endoscopy with bronchial aspiration and BAL are needed. Sputum and tracheal aspiration can be realized when it is possible. CT-guided percutaneous biopsy should be performed when BAL is non-diagnostic, but this procedure is contra-indicated in patients with platelets below 50,000/mm3 . In a se3 . BiopsieMucorales are identified by macroscopic and microscopic examination  Figure . The typAspergillus species [Histology can show hyphae that have the characteristics of Mucorales as described before, using haematoxylin-eosin (HE), periodic acid-Schiff stain (PAS), or Grocott-Gomori’s methenamine-silver (GMS) staining, or both  Figure . Immunoh species ,94,95. I species . These n species ,90,97. I species . NeutropLichtheimia, Rhizomucor and Mucor/Rhizopus in serum has shown promising preliminary results [®, PathoNostics) detects the species from the five most frequent genera, Rhizopus, Mucor, Lichtheimia, Cunninghamella, and Rhizomucor, but cannot distinguish between them [Aspergillus PCR [A PCR-Based diagnosis in serum has been developed by different teams . A quant results ,100. It  results . The per results . In foureen them . Springeeen them . All qPCeen them . They arllus PCR .Mucor, Rhizopus, Aspergillus, Fusarium, and Candida species has been constructed as a lateral flow assay [Rhizopus arrhizus, has been set up and is compatible with serum and bronchoalveolar fluid [Rhizopus-specific antigen in serum and BAL fluid. Primary results showed higher level of antigen in patients with mucormycosis compared to controls [CotH genes are uniquely present among Mucorales and are potential targets for the diagnosis of mucormycosis. CotH genes were detected by PCR in urine samples from mice infected by different species of Mucorales. The sensitivity and specificity were 90% and 100%, respectively. They were also detected in the urine samples of patients with proven mucormycosis [R. arrhizus, R. delemar and R microsporus) from each other in a murine model. These new biomarkers are promising but need prospective validation in human samples.Among biomarkers, β-D-glucan and galactomannan antigen are not present or are present in low amounts in the cell wall of Mucorales. They are not detected in the serum of patients with mucormycosis. Novel diagnostic approaches have recently been developed. The detection of a panfungal disaccharide, which turned out to be trehalose, using mass spectrometry, was detected in the serum of 9/16 patients with mucormycosis . A monocow assay . Anotherar fluid . Anothercontrols . CotH germycosis . The anaWhat should be remembered? Every effort should be made to obtain specimens on which to perform direct examination, cultures, and histopathology. Serum qPCR is a non-invasive sensitive and specific test for the diagnosis of mucormycosis. Novel diagnostic approaches are in development.The treatment of mucormycosis relies on three key elements, which are antifungal treatment, correction of risk factor(s), and surgery. No prospective comparative studies have been performed in this rare infection and no one has specifically studied the treatment of PM.Prompt antifungal therapy initiation is critical as delay in initiation is associated with increase in mortality. Delaying the initiation of amphotericin B (AmB) for more than three days increased mortality (72 vs. 33%) . A seconLiposomal amphotericin B (L-AmB) is the recommended first-line treatment for mucormycosis at a dose of 5–10 mg/kg/day . EvidencMucor species, notably for Mucor circinelloides [Isavuconazole is a triazole, active in vitro against a majority of Mucorales. Its in vitro activity appears to be species-specific, and it shows reduced activity against elloides ,113,114.elloides . Based oelloides ,117. Morelloides .Mucor circinelloides [Posaconazole is also active in vitro against a majority of Mucorales. Of note, some isolates exhibit high MIC, notably elloides ,113,114.elloides ,120 but elloides ,121. On elloides ,122,123.elloides ,125.The therapeutic range of isavuconazole and posaconazole for mucormycosis is unknown. Therapeutic drug monitoring is recommended for posaconazole therapy due to high intra- and inter-individual variability and non-linear pharmacokinetics. The target concentration is >1 µg/mL . On the Isavuconazole and posaconazole are inhibitors of CYP3A4 resulting in drug-drug interactions. Online websites can be helpful for quantitative prediction of drug-drug interaction. Therefore, dosage of immunosuppressive treatments which are metabolized by cytochrome P450 should be adapted during treatment. Other drug-drug interactions, including membrane transporters inhibition, can occur and therapeutic drug monitoring of immunosuppressive treatments is mandatory.R. arrhizus, in the same manner as isavuconazole, when tested against infecting strains with both low (0.25 µg/mL) and elevated (4 µg/mL) MECs [Among new antifungal drugs, fosmanogepix APX001 targets glycosylphosphatidylinositol-anchored protein maturation by inhibiting the fungal enzyme Gwt1. In vitro antifungal activity of fosmanogepix against most Mucorales is limited (minimum effective concentration (MEC)90, 4–16 µg/mL), but some isolates have low MEC (<1 µg/mL) ,131. In mL) MECs . IbrexafmL) MECs .Rhizopus arrhizus β-1,3-D-glucan synthase and an improvement of survival in mice model but only at low dose [R. arrhizus var delemar, a species with low MECs to fosmanogepix, mice treated by a combination of fosmanogepix and liposomal amphotericin B had a survival of 70%, greater than mice treated with fosmanogepix (30%), liposomal amphotericin B (35%), or receiving a placebo (5%) [Although it was not recommended in recent guidance, the interest of a combined therapy as first line to improve the survival remains an open question ,133. In low dose . On the low dose ,139,140.low dose . The rollow dose ,142. Thelow dose ,144. Finebo (5%) .R. delemar invasion of alveolar epithelial cells and protected mice from pulmonary mucormycosis [Among adjunctive treatments, deferasirox has failed to demonstrate a benefit, at least in patients with HM . Hyperbarmycosis .Recent guidance from the European Confederation of Medical Mycology and the Mycoses Study Group Education and Research Consortium recommend a first-line therapy with liposomal amphotericin B . When thSummary of PM management from our group .The initial treatment is based on L-AmB. The correction of risk factors, if feasible, is also a critical point, including control of DM, correction of neutropenia and ketoacidosis, and decrease of immunosuppressants. In COVID-associated mucormycosis, dexamethasone and anti-IL6, given for the viral disease, should be tapered or stopped if possible. Therapeutic response should be assessed by a lung CT scan after one, two and four weeks of treatment and by mycological samples on respiratory samples if feasible and serum PCR. Reevaluation at week 1 should be done with caution; a paradoxical worsening is possible after neutrophil recovery and should not be considered progression of the disease. The duration of the first-line therapy is at least two weeks but may require four weeks or more. After radiological stabilization or partial response, in association with negative mycological samples, step-down therapy with oral isavuconazole or posaconazole can be started. The duration of the treatment is highly variable but needs to be continued until complete clinical and radiological responses. Finally, secondary prophylaxis  with oral azole should be discussed when there is any risk of relapse during persistence of immune defect including neutropenia, chemotherapy, or prolonged use of high-dose immunosuppressive therapy. Further studies are warranted to identify risk factors of relapse to better target patients who require prolonged maintenance therapy.n = 3), altered mental state (n = 1), rapid death after diagnosis (n = 1)) and refusal of the patients because of concern for operative risk (n = 4) [Recent recommendations strongly support an early surgical treatment for mucormycosis in addition to systemic antifungal treatment . Three l (n = 4) . MoreoveWhat should be remembered? Liposomal amphotericin B is the first line of treatment for mucormycosis in association with the correction of underlying disease and surgery when feasible. Step-down treatment includes oral isavuconazole and posaconazole delayed release tablets.Mortality depends on the site of involvement in mucormycosis. PM and disseminated forms are associated with lower survival than other forms. In the Retrozygo study, mortality in PM and disseminated forms were 48% and 79% compared to 25 and 22% in rhinocerebral and cutaneous forms, respectively . MortaliAPACHE II score, severe lymphocytopenia and high LDH levels have been identified as prognostic factors in patients with HM and PM . AnotherProgress has been made in the last decade to improve knowledge of the pathophysiology, the diagnosis, notably via the development of non-invasive PCR in serum, and the treatment of PM. Despite that, mortality remains high; future research must focus on the role of combined therapy, surgery and adjunctive therapy, and the development of new antifungal drugs.Conceptualization, F.D. and O.L. F.D. wrote the first draft of the manuscript. F.D., V.A. and D.G.-H. prepared the figures. All authors carefully reviewed the paper. All authors have read and agreed to the published version of the manuscript.


To the Editor,Current treatments for age-related macular degeneration (AMD) —the primary cause of visual impairment in western countries in people over 50 — are limLacticaseibacillus casei (L. casei) strain BL23 and time-restricted feeding intervention to modulate the PUFA content in the mouse retina.Changes in the gut microbiota of AMD patients have been reported and several experimental studies suggest the existence of a gut-retina axis, in which gut microbes would influence AMD-associated mechanisms  and modulate retina physiology, including its lipid composition . Approacad libitum group) whereas the other had a time-restricted access to food  group, [L. casei BL23 by daily oral gavage   Prevotellaceae —a family including producers of short chain fatty acids that are metabolites regulating of host lipid metabolism and health [L. casei-supplemented mice; (ii) Lactobacillaceae —a family including species having probiotic potential [Eggerthellaceae —a family with members involved in the production of health-promoting metabolites (urolithins) [L. casei  was significantly increased in mice supplemented with fed mice . A trendfed mice . Linear d health — in L. cotential — in ITADlithins) — in ITADL. casei .L. casei supplementation deeply impacted lipids in the retina by significantly enriching its PUFA content  / total DMAs  ratio and the increased abundance of 2 DMA species (The combination of ITAD feeding with  content . The hig content . At the fed-mice . Particuted mice . Moreove species . PlasmalL. casei supplementation alone or in combination with ITAD feeding significantly reduced the n-6/n-3 ratio in mouse retinas as well as that of ARA/DHA, which are the most abundant retinal n-6 and n-3 PUFAs (L. casei (L. casei (An excessive amount of n-6 PUFAs and a high n-6/n-3 ratio are promoting factors for many diseases including AMD . We obse-3 PUFAs . This phL. casei . InteresL. casei .In conclusion, this study provides evidence that time-restricted feeding combined to probiotics is a promising strategy to modulate retinal DHA content, and thus to sustain retinal homeostasis during aging. Further investigations are needed to decipher the molecular mechanisms involved in the microbiota-retina dialogue, as well as to evaluate the efficacy of such a strategy in protecting the retina against pathophysiological mechanisms related to AMD.www.aginganddisease.org/EN/10.14336/AD.2023.0324.The Supplementary data can be found online at: