The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.

BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

Robust Low-Friction and Low-Wear TiNbMoTaCr High-Entropy Film Enabled by Periodically Inserting Curved MoS2 Sheets.

The well-known integration of physical, chemical, and mechanical properties enables high-entropy alloys (HEAs) to be applied in various fields; however, refractory HEAs are brittle and susceptible to abrasive wear at high coefficients of friction (COF), resulting in insufficient mechanical durability against abrasion. Herein, curved MoS2 nanosheets are periodically introduced into the TiNbMoTaCr film for triggering the self-assembly mixed metal oxides @MoS2 nanoscrolls, which contain hard mixed metal oxides cores and the low-shearing lubricant MoS2 shells, during the friction in the air environment; such mixed metal oxides@MoS2 nanoscrolls in the friction interfaces can contribute to the robust low friction and low wear. Compared to the pure TiNbMoTaCr film (with high COF of ∼0.78, low abrasive durability identified by worn-out event), the periodic incorporation of 10 nm thickness curved MoS2 sheets can successfully achieve a low COF of ∼0.08 and low wear rate of ∼9.561 × 10-8 mm3/ Nm, much lower than the pure MoS2 film (COF = ∼ 0.21, wear rate = ∼ 1.03 × 10-6 mm3/ Nm). Such superior tribological properties originate from the cooperative interaction of TiNbMoTaCr nanolayers and curved MoS2 nanosheets, accompanied by the self-assembly of mixed metal oxides@MoS2 nanoscrolls. In these nanoscrolls, TiNbMoTaCr can act as an 'air-absorbing agent' to form high-loading mixed metal oxide cores and serve as an 'oxygen sacrificer,' preventing the low-shearing lubricant curved MoS2 nanosheets from oxidation. In addition, even with the soft MoS2, the hardness of the TiNbMoTaCr/MoS2 nanomultilayers can still be well maintained and increased above the calculated values by mixing law, further favoring superior mechanical durability. The synergetic effect of TiNbMoTaCr and curved MoS2 nanosheets during the friction in air can provide a route to design HEA films with enhanced tribological properties for better mechanical durability and broader application prospects.

Helicobacter pylori infection prevalence declined among an urban health check-up population in Chengdu, China: a longitudinal analysis of multiple cross-sectional studies.

Objectives: The efficacy of updated health policy in improving the generalization of Helicobacter pylori screening and eradication in southwest China was assessed in a longitudinal analysis of multiple cross-sectional studies from an institution. Methods: In the periods 2009-2010, 2013-2014, and 2019-2021, 8,365, 16,914, and 18,281 urban observations from health check-ups at West China Hospital were analyzed, respectively. The 14C-urea or 13C-urea breath test was consistently used for H. pylori detection. The protocol has been reported elsewhere (PROSPERO Registration number: CRD42019120764). Results: The overall prevalence of H. pylori dramatically decreased from 53.1% to 30.7% over the past decade (OR = 0.39, 95% CI 0.37-0.41), with a similar decline in all sex-specific and age-specific subgroups. The age-specific prevalence consistently increased before 40 years of age and always peaked at 50-59 years. Longitudinal clearance increased along with aging, and prevalence dropped to 22.6%, 25.1%, and 23.6% in the 40-49, 50-59, and 60-69 years initial age groups, respectively. Conclusion: The generalization of H. pylori screening and eradication could greatly contribute to the control of H. pylori infection among urban health check-up populations and lower gastric cancer incidence.

Chemical Constituents and α-Glucosidase Inhibitory, Antioxidant and Hepatoprotective Activities of Ampelopsis grossedentata.

Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids (1-2) and seventeen known compounds (3-19) were isolated and identified from the dried stems and leaves of A. grossedentata. These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their α-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure-activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against α-glucosidase, with an IC50 value of 0.21 µM. In addition, compounds 1-2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions.

Bamboo-like dual-phase nanostructured copper composite strengthened by amorphous boron framework.

Grain boundary engineering is a versatile tool for strengthening materials by tuning the composition and bonding structure at the interface of neighboring crystallites, and this method holds special significance for materials composed of small nanograins where the ultimate strength is dominated by grain boundary instead of dislocation motion. Here, we report a large strengthening of a nanocolumnar copper film that comprises columnar nanograins embedded in a bamboo-like boron framework synthesized by magnetron sputtering co-deposition, reaching the high nanoindentation hardness of 10.8 GPa among copper alloys. The boron framework surrounding copper nanograins stabilizes and strengthens the nanocolumnar copper film under indentation, benefiting from the high strength of the amorphous boron framework and the constrained deformation of copper nanocolumns confined by the boron grain boundary. These findings open a new avenue for strengthening metals via construction of dual-phase nanocomposites comprising metal nanograins embedded in a strong and confining light-element grain boundary framework.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

Pt-induced atomic-level tailoring towards paracrystalline high-entropy alloy.

Paracrystalline state achieved in the diamond system guides a direction to explore the missing link between amorphous and crystalline states. However, such a state is still challenging to reach in alloy systems in a controlled manner. Here, based on the vast composition space and the complex atomic interactions in the high-entropy alloys (HEAs), we present an "atomic-level tailoring" strategy to create the paracrystalline HEA. The addition of atomic-level Pt with the large and negative mixing enthalpy induces the local atomic reshuffling around Pt atoms for the well-targeted local amorphization, which separates severe-distorted crystalline Zr-Nb-Hf-Ta-Mo HEA into the high-density crystalline MRO motifs on atomic-level. The paracrystalline HEA exhibits high hardness (16.6 GPa) and high yield strength (8.37 GPa) and deforms by nanoscale shear-banding and nanocrystallization modes. Such an enthalpy-guided strategy in HEAs can provide the atomic-level tailoring ability to purposefully regulate structural characteristics and desirable properties.

Alterations of Plasma Lipids in Adult Women With Major Depressive Disorder and Bipolar Depression.

Lipidomics has been established as a potential tool for the investigation of mental diseases. However, the composition analysis and the comparison of the peripheral lipids regarding adult women with major depressive depression (MDD) or bipolar depression (BPD) has been poorly addressed. In the present study, age-matched female individuals with MDD (n = 28), BPD (n = 22) and healthy controls (HC, n = 25) were enrolled. Clinical symptoms were assessed and the plasma samples were analyzed by comprehensive lipid profiling based on liquid chromatography-mass spectrometry (LC/MS). We found that the composition of lipids was remarkably changed in the patients with MDD and BPD when compared to HC or compared to each other. Moreover, we identified diagnostic potential biomarkers comprising 20 lipids that can distinguish MDD from HC (area under the curve, AUC = 0.897) and 8 lipids that can distinguish BPD from HC (AUC = 0.784), as well as 13 lipids were identified to distinguish MDD from BPD with moderate reliability (AUC = 0.860). This study provides further understanding of abnormal lipid metabolism in adult women with MDD and BPD and may develop lipid classifiers able to effectively discriminate MDD from BPD and HC.

Aponeurosis discission, a low-detergent method for tissue-engineered acellular ligament scaffolds.

Detergent treatment is the most commonly used method for the decellularization of ligaments and tendon grafts. However, it is well recognized that detergent treatment can also adversely affect the extracellular matrix. This study found that discission into the aponeurosis layer of the patellar tendon (PT) before decellularization is conducive to extracting cells from the PT using a low quantity of detergent in a short time period. The acellular aponeurosis discission ligament (AADL) retains its native collagen fibril structure and mechanical properties. Moreover, the PT retained cell and tissue compatibility in vitro and in vivo. After implantation into a defective allogeneic PT, we found that the AADL healed well in the host, and its collagen structure exhibited gradual improvement 12 months after implantation with satisfactory reconstruction. IMPACT: The aponeurosis of tendons/ligaments is the main barrier to achieving complete decellularization, and it thus prevents complete recellularization for applications in tissue engineering. Aponeurosis can obstruct the removal of cell components. We found that excising the aponeurosis before decellularization allows for the removal of cellular components with a reduced amount of detergent, thus improving the biological properties of the acellular ligament. To the best of our knowledge, no similar studies have been performed. Graphical abstract.

The traditional ethnic herb Tadehagi triquetrum from China: a review of its phytochemistry and pharmacological activities.

CONTEXT: Tadehagi triquetrum (Linn.) Ohashi (Fabaceae) (TT), is a traditional herbal medicine used especially in China's ethnic-minority communities, such as the Zhuang, Dai, Li and Wa aeras. As an ethnic medicine, it has long been used to treat various diseases. OBJECTIVE: This review summarised the phytochemical and pharmacological progress on TT from 1979 to October, 2021 by highlighting its chemical classification, structural features, pharmacological applications and folk applications to provide inspirations and suggestions for accelerating further research of this traditional phytomedicine. METHODS: The information on TT in this article has been obtained using these multiple scientific databases including Scifinder, Web of Science, ScienceDirect, Wiley, ACS publications, Springer, PubMed, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar and Baidu Scholar. Some information was also collected from classic literature on traditional Chinese medicines. RESULTS: More than 70 compounds have been isolated and reported from TT to date by the comprehensive analysis of the current literature. A large number of traditional uses and pharmacological studies have exhibited diversified bioactivities of various TT extracts and its metabolites, including anti-inflammatory, antimicrobial, anti-hepatitis B virus, hepatoprotective, insecticidal, etc. CONCLUSIONS: As a famous traditional medicine with a long history, TT has various medicinal uses and some of them have been supported by modern pharmacological researches. Further detailed studies on the action mechanisms, pharmacodynamics and structure-function relationships of single compounds or active constituents from TT are also required.

Effect of Jiedu Huayu Granules on Inflammatory State of Patients with Chronic Hepatic Failure with Toxic Heat and Stasis Syndrome / 中国实验方剂学杂志

ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ2=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ2=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.

Molecular epidemiological characteristics of the virus in 96 children with acute diarrhea in Changdu of Tibet, China / 中国当代儿科杂志

OBJECTIVES@#To study the molecular epidemiological characteristics of the virus in children with acute viral diarrhea in Changdu of Tibet, China.@*METHODS@#Fecal specimens were collected from 96 children with acute diarrhea who visited the People's Hospital of Changdu, Tibet, from November 2018 to November 2020 and were tested for adenovirus, norovirus, astrovirus, sapovirus, and rotavirus. Gene sequencing was performed for the genotypes of these viruses.@*RESULTS@#The overall positive rate of the five viruses was 39% (37/96), among which astrovirus had the highest positive rate of 17%, followed by norovirus (9%), rotavirus (8%), adenovirus (7%), and sapovirus (5%). There was no significant difference in the positive rate of the five viruses among different age groups (P>0.05). Only the positive rate of astrovirus was significantly different among the four seasons (P<0.05). For adenovirus, 6 children had F41 type and 1 had C2 type; for norovirus, 6 had GⅠ.3 type, 1 had GⅠ.7 type, 1 had GⅡ.3 type, and 2 had GⅡ.4 Sydney_2012 type; HAstrV-1 type was observed in all children with astrovirus infection; for sapovirus, 1 child each had sporadic GⅠ.2, GⅠ.6, and GⅡ.1 sapovirus and 2 children had unknown type; 6 children had rotavirus G9[P8].@*CONCLUSIONS@#Astrovirus and norovirus are important pathogens in children with acute diarrhea in Changdu, Tibet. The positive rate of adenovirus, norovirus, astrovirus, sapovirus, and rotavirus is not associated with age, and only the positive rate of astrovirus has obvious seasonality. F41 type is the dominant genotype of adenovirus; GⅠ.3 is the dominant genotype of norovirus; HAstrV-1 is the dominant genotype of astrovirus; sporadic GⅠ.2, GⅠ.6, and GⅡ.1 are the dominant genotypes of sapovirus; G9[P8] is the dominant genotype of rotavirus.

The Levels of Inflammatory Regulatory Factors in Acute Leukemia Complicated by Infection and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To explore the expression levels and clinical significance of helper T cell 1/helper T cell 2 (Th1/Th2) cytokine and interleukin-6 (IL-6) in patients with acute leukemia (AL) complicated by infection.@*METHODS@#68 patients with AL complicated by infection admitted to Wuhan Fifth Hospital from May 2017 to January 2020 were enrolled as study group, 50 AL patients without infection were enrolled as AL group, and 30 healthy volunteers checked in physical examination center were enrolled as healthy control group. The levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), and peripheral blood Th1/Th2 cells subsets were measured and compared among the three groups. The serum IL-6, IL-10, TNF-α and Th1/Th2 were compared between the patients with mild to moderate infection (n=52) and septic shock (n=16). The relationship between IL-6, IL-10, TNF-α, Th1/Th2 and AL infection was analyzed.@*RESULTS@#The levels of IL-6, IL-10 , TNF-α, and the proportion of Th2 of the patients in study group and AL group were significantly higher than those in healthy control group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in healthy control group (P<0.001). The levels of IL-6, IL-10 and TNF-α, and the proportion of Th2 the patients in study group were significantly higher than those in AL group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in AL group (P<0.001). The serum IL-6, IL-10 and TNF-α level of the patients in septic shock group were significantly higher than those in mild-to-moderate infection group (P<0.001), while Th1/Th2 was lower than those in mild-to-moderate infection group (P<0.001). The results of ROC curve analysis showed that the area under the ROC curve (AUC) values of IL-6, IL-10, TNF-α and Th1/Th2 alone for the diagnosis of septic shock were 0.779, 0.761, 0.724 and 0.718, which were lower than that their combination (0.910) (P<0.05).@*CONCLUSION@#The levels of serum IL-6, IL-10 and TNF-α are high in patients with AL complicated infection and septic shock, while Th1/Th2 cell subsets is low. The combined detection of serum IL-6, IL-10, TNF-α and Th1/Th2 is a good diagnostic value for predicting the occurrence of severe septic shock.

Content Difference of Effective Components of Cynomorii Herba Between Different Producing Areas and Its Response to Environmental Factors / 中国实验方剂学杂志

ObjectiveTo explore the content difference of gallic acid，protocatechuic acid，catechin，total flavonoids， and total polysaccharides in Cynomorii Herba between different producing areas and the correlation between effective components and environmental factors. MethodNinety-five batches of Cynomorii Herba samples were collected from 12 major producing areas in five provinces （autonomous regions）， including Gansu，Inner Mongolia，Xinjiang，Qinghai， and Ningxia，and the geographical-climatic factors such as altitude，longitude and latitude，climate type，annual average frost-free period，annual rainfall，annual sunshine hours，annual average temperature， and annual average evaporation were recorded. The content of gallic acid，protocatechuic acid， and catechin in Cynomorii Herba was determined by high-performance liquid chromatography （HPLC），and the mathematical model of the correlation between the content of chemical components and environmental factors was optimized and established. ResultPearson correlation analysis showed that protocatechuic acid content in Cynomorii Herba increased with the increase in annual average frost-free period and annual average temperature， and catechin content increased with the increase in the annual average frost-free period，annual sunshine hours， and annual average evaporation，while total polysaccharides content decreased with the increase in altitude. Redundancy analysis （RDA） showed that the annual average frost-free period， annual average evaporation，annual sunshine hours， and altitude had great influences on the content of effective components in Cynomorii Herba. Curve fitting showed that the optimal conditions for the growth of Cynomorii Herba were as follows： altitude of 800-2 000 m，annual average frost-free period of 80-110 d， annual rainfall of 110-300 mm，annual sunshine hours of 2 400-3 000 h， annual average temperature of 2.2-8.8 ℃，and annual average evaporation of 1 700-2 500 mm. ConclusionThe content of effective components in Cynomorii Herba is diverse in terms of producing areas and shows a clear response rule to environmental factors. The areas suitable for growing and artificial cultivation introduction are those with high altitude，short annual average frost-free period，low annual rainfall，large average evaporation，long sunshine hours， and low annual average temperature.

Panax notoginseng Saponins Alleviate TGF-β1-induced Renal Tubular Epithelial Cell Injury by Inhibiting Autophagy / 中国实验方剂学杂志

ObjectiveTo investigate the role and mechanism of Panax notoginseng saponins （PNS） in inhibiting transforming growth factor-β1 （TGF-β1）-induced renal tubular epithelial cell injury. MethodNRK-52E renal tubular epithelial cells were cultured and divided into control group， TGF-β1 group，TGF-β1+12.5 mg·L-1 PNS group，TGF-β1+25 mg·L-1 PNS group and TGF-β1+50 mg·L-1 PNS group. After 48 hours of PNS intervention， the cells and the supernatant were collected， and cell morphology was observed by inverted microscope. Western blot was used to detect the expression of epithelial-mesenchymal transition （EMT）-related proteins and autophagy-related proteins. Flow liquid chromatography for multiple protein quantification and flow cytometry were employed to determine the content of inflammatory factors and apoptosis rate， respectively. ResultCompared with the conditions in the control group， after TGF-β1 induction， the cells showed a spindle-shaped change and the expression of E-cadherin was down-regulated （P<0.05）， while the expression of α-smooth muscle actin （α-SMA） was up-regulated （P<0.05）. After PNS treatment， most of the cells tended to be normal and reversed the occurrence of EMT. In addition， compared with the conditions in the control group， the level of TNF-α was increased while that of IL-10 was decreased， with elevated apoptosis rate （P<0.05） in the TGF-β1 group. After PNS treatment， the level of TNF-α was lowered while that of IL-10 was boosted with the increase of the dose， with reduced apoptosis rate （P<0.05）. Moreover， after TGF-β1 induction， the expression of autophagy-related proteins Beclin 1 and LC3Ⅱ/Ⅰ in renal tubular epithelial cells were up-regulated， while PNS inhibited their expression（P<0.05，P<0.01）. ConclusionPNS had a protective effect on TGF-β1-induced renal tubular epithelial cells， and the mechanism might be that it reduced inflammation and apoptosis by inhibiting autophagy， thus alleviating TGF-β1-induced injury.

Instability of Hyperthermia Temperature for Magnetic Nanoparticles of Low Anisotropy Constant Due to Nonlinear Characteristics.

Magnetic nanoparticles (MNPs) subjected to external alternating magnetic field can induce heat in MNPs due to hysteresis, which is usually employed for tumor hyperthermia. An effective hyperthermia treatment should selectively kill the tumor cells without damaging the ambient healthy tissue. Hence, it is important for hyperthermia to correctly control the alternating magnetic field-induced temperature of MNPs in the tumor. This work develops a thermal model to analyze various forms of temperature-rise with time in magnetic nanoparticles for tumor hyperthermia. Results show that there are horizontal, linear rise, square root, exponential decay and abrupt temperature-rise lines with time in MNPs. The horizontal, linear rise, and square root temperature lines with time are consistent with the available experimental data. It is worthily noted that the form of abrupt temperaturerise with time can result in harm to the normal cells or tissue. If the abrupt temperature-rise does not be controlled and predicted well.

Genetic variants of cell cycle pathway genes are associated with head and neck squamous cell carcinoma in the Chinese population.

Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case-control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (Ptrend < 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T>C reduced the stability of E2F2 3'-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e-8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02-1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3, and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells.

Electronic metal-support interaction modulates single-atom platinum catalysis for hydrogen evolution reaction.

Tuning metal-support interaction has been considered as an effective approach to modulate the electronic structure and catalytic activity of supported metal catalysts. At the atomic level, the understanding of the structure-activity relationship still remains obscure in heterogeneous catalysis, such as the conversion of water (alkaline) or hydronium ions (acid) to hydrogen (hydrogen evolution reaction, HER). Here, we reveal that the fine control over the oxidation states of single-atom Pt catalysts through electronic metal-support interaction significantly modulates the catalytic activities in either acidic or alkaline HER. Combined with detailed spectroscopic and electrochemical characterizations, the structure-activity relationship is established by correlating the acidic/alkaline HER activity with the average oxidation state of single-atom Pt and the Pt-H/Pt-OH interaction. This study sheds light on the atomic-level mechanistic understanding of acidic and alkaline HER, and further provides guidelines for the rational design of high-performance single-atom catalysts.