Time series analysis of using the PDCA method combined with the Teach-back method to improve spontaneous reports of adverse drug reactions in a grade IIIA hospital in China.

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) is essential for the post-marketing safety evaluation of drugs. Therefore, good monitoring of ADRs is vital for strengthening drug supervision, management, and guiding rational drug use. Chinese medical institutions are the primary source of ADR case reports, but the proportion of the reports in grade IIIA hospitals is still low due to serious under-reporting. The 3rd Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People's Hospital, also has such a problem. OBJECTIVE: To improve the quantity and quality of ADR reports and enhance the level of pharmacovigilance in hospitals, the Third Affiliated Hospital of Chengdu Medical College, People's Hospital of Chengdu Pidu District experienced 10 years to gradually establish a management model to improve the medical staff's reporting rate of spontaneous reporting of ADRs. The management model is led by clinical pharmacists and combines the PDCA with Teach-back methods. The purpose of this paper is to introduce the management model and discuss its advantages and shortcomings of this model. METHODS: This study was conducted at the Third Affiliated Hospital of Chengdu Medical College-Chengdu Pidu District People's Hospital. From 2016, the daily management of reporting, auditing, and data improvement of adverse drug reactions in the hospital was carried out by clinical pharmacists, who used the PDCA method combined with the Teach-back method to continuously improve the reporting program of ADRs in the hospital during 2016-2021. Then, the proportion of spontaneous reports of total, new, and serious ADRs was compared before and after the intervention. Also, we performed a time series analysis using an autoregressive moving average model to assess changes in the total number of spontaneous ADR reports before the intervention (2013-2015), the first intervention (2016-2018), and the second intervention (2019-2021). RESULTS: After the combined PDCA and Teach-back method intervention, the median number of reported ADRs per year increased from 50 (range 37-55) in the pre-intervention period to 88 (range 83-162) in the first intervention period and to 374 in the second (range 312-566). Breakpoint regression analysis of the spontaneous reporting rate of ADRs showed that the instantaneous increase after the first intervention was not statistically significant (P = 0.526). However, the reporting rate of ADRs increased at a month-by-month growth rate during the second intervention compared to the first intervention. Its spontaneous reporting rate improved 1.034 times (P = 0.002). After the second intervention, the spontaneous reporting rate of ADRs transiently increased 6.111-fold (P < 0.001), and the month-to-month growth rate increased 1.024-fold (P < 0.001) again. CONCLUSION: The management model that combines the PDCA and the Teach-back method significantly improves the reporting rate of adverse drug reactions.

Bifunctional K3PW12O40/Graphene Oxide-Modified Separator for Inhibiting Polysulfide Diffusion and Stabilizing Lithium Anode.

Lithium-sulfur (Li-S) batteries are considered as promising candidates for next-generation batteries due to their high theoretical energy density. However, the practical application of Li-S batteries is still hindered by several challenges, such as the polysulfide shuttle and the growth of lithium dendrites. Herein, we introduce a bifunctional K3PW12O40/graphene oxide-modified polypropylene separator (KPW/GO/PP) as a highly effective solution for mitigating polysulfide diffusion and protecting the lithium anode in Li-S batteries. By incorporating KPW into a densely stacked nanostructured graphene oxide (GO) barrier membrane, we synergistically capture and rapidly convert lithium polysulfides (LiPSs) electrochemically, thus effectively suppressing the shuttling effect. Moreover, the KPW/GO/PP separator can stabilize the lithium metal anode during cycling, suppress dendrite formation, and ensure a smooth and dense lithium metal surface, owing to regulated Li+ flux and uniform Li nucleation. Consequently, the constructed KPW/GO/PP separator delivered a favorable initial specific capacity (1006 mAh g-1) and remarkable cycling performance at 1.0 C (626 mAh g-1 for up to 500 cycles with a decay rate of 0.075% per cycle).

Does PM1 exposure during pregnancy impact the gut microbiota of mothers and neonates?

BACKGROUND: Ambient air pollutant exposure can change the composition of gut microbiota at 6-months of age, but there is no epidemiological evidence on the impacts of exposure to particulate matter with an aerodynamic diameter ≤1 µm (PM1) during pregnancy on gut microbiota in mothers and neonates. We aimed to determine if gestational PM1 exposure is associated with the gut microbiota of mothers and neonates. METHODS: Leveraging a mother-infant cohort from the central region of China, we estimated the exposure concentrations of PM1 during pregnancy based on residential address records. The gut microbiota of mothers and neonates was analyzed using 16 S rRNA V3-V4 gene sequences. Functional pathway analyses of 16 S rRNA V3-V4 bacterial communities were conducted using Tax4fun. The impact of PM1 exposure on α-diversity, composition, and function of gut microbiota in mothers and neonates was evaluated using multiple linear regression, controlling for nitrogen dioxide (NO2) and ozone (O3). Permutation multivariate analysis of variance (PERMANOVA) was used to analyze the interpretation degree of PM1 on the sample differences at the OTU level using the Bray-Curtis distance algorithm. RESULTS: Gestational PM1 exposure was positively associated with the α-diversity of gut microbiota in neonates and explained 14.8% (adj. P = 0.026) of the differences in community composition among neonatal samples. In contrast, gestational PM1 exposure had no impact on the α- and ß-diversity of gut microbiota in mothers. Gestational PM1 exposure was positively associated with phylum Actinobacteria of gut microbiota in mothers, and genera Clostridium_sensu_stricto_1, Streptococcus, Faecalibacterium of gut microbiota in neonates. At Kyoto Encyclopedia of Genes and Genomes pathway level 3, the functional analysis results showed that gestational PM1 exposure significantly down-regulated Nitrogen metabolism in mothers, as well as Two-component system and Pyruvate metabolism in neonates. While Purine metabolism, Aminoacyl-tRNA biosynthesis, Pyrimidine metabolism, and Ribosome in neonates were significantly up-regulated. CONCLUSIONS: Our study provides the first evidence that exposure to PM1 has a significant impact on the gut microbiota of mothers and neonates, especially on the diversity, composition, and function of neonatal meconium microbiota, which may have important significance for maternal health management in the future.

Soybean GmSAUL1, a Bona Fide U-Box E3 Ligase, Negatively Regulates Immunity Likely through Repressing the Activation of GmMPK3.

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, suggesting that the activation of GmMPK3 is most likely responsible for the activated immunity observed in the GmSAUL1a/1b-silenced plants. Furthermore, we provided evidence that GmSAUL1a is a bona fide E3 ligase. Collectively, our results indicated that GmSAUL1 plays a negative role in regulating cell death and immunity in soybean.

Hemolytic Activity in Relation to the Photosynthetic System in Chattonella marina and Chattonella ovata.

Chattonella species, C. marina and C. ovata, are harmful raphidophycean flagellates known to have hemolytic effects on many marine organisms and resulting in massive ecological damage worldwide. However, knowledge of the toxigenic mechanism of these ichthyotoxic flagellates is still limited. Light was reported to be responsible for the hemolytic activity (HA) of Chattonella species. Therefore, the response of photoprotective, photosynthetic accessory pigments, the photosystem II (PSII) electron transport chain, as well as HA were investigated in non-axenic C. marina and C. ovata cultures under variable environmental conditions (light, iron and addition of photosynthetic inhibitors). HA and hydrogen peroxide (H2O2) were quantified using erythrocytes and pHPA assay. Results confirmed that% HA of Chattonella was initiated by light, but was not always elicited during cell division. Exponential growth of C. marina and C. ovata under the light over 100 µmol m-2 s-1 or iron-sufficient conditions elicited high hemolytic activity. Inhibitors of PSII reduced the HA of C. marina, but had no effect on C. ovata. The toxicological response indicated that HA in Chattonella was not associated with the photoprotective system, i.e., xanthophyll cycle and regulation of reactive oxygen species, nor the PSII electron transport chain, but most likely occurred during energy transport through the light-harvesting antenna pigments. A positive, highly significant relationship between HA and chlorophyll (chl) biosynthesis pigments, especially chl c2 and chl a, in both species, indicated that hemolytic toxin may be generated during electron/energy transfer through the chl c2 biosynthesis pathway.

Silencing Autophagy-Related Gene 2 (ATG2) Results in Accelerated Senescence and Enhanced Immunity in Soybean.

Autophagy plays a critical role in nutrient recycling and stress adaptations. However, the role of autophagy has not been extensively investigated in crop plants. In this study, soybean autophagy-related gene 2 (GmATG2) was silenced, using virus-induced silencing (VIGS) mediated by Bean pod mottle virus (BPMV). An accelerated senescence phenotype was exclusively observed for the GmATG2-silenced plants under dark conditions. In addition, significantly increased accumulation of both ROS and SA as well as a significantly induced expression of the pathogenesis-related gene 1 (PR1) were also observed on the leaves of the GmATG2-silenced plants, indicating an activated immune response. Consistent with this, GmATG2-silenced plants exhibited a significantly enhanced resistance to Pseudomonas syringae pv. glycinea (Psg) relative to empty vector control plants (BPMV-0). Notably, the activated immunity of the GmATG2-silenced plants was independent of the MAPK signaling pathway. The fact that the accumulation levels of ATG8 protein and poly-ubiquitinated proteins were significantly increased in the dark-treated GmATG2-silenced plants relative to the BPMV-0 plants indicated that the autophagic degradation is compromised in the GmATG2-silenced plants. Together, our results indicated that silencing GmATG2 compromises the autophagy pathway, and the autophagy pathway is conserved in different plant species.

[Progress in application of Bletilla striata polysaccharide in novel drug delivery systems and biomaterials].

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.

Pharmacokinetics and safety of PC-SOD, a lecithinized recombinant superoxide dismutase, in healthy Chinese subjects: A phase 1, randomized, placebo-controlled, dose-escalation study
.

OBJECTIVES: To evaluate the pharmacokinetics of PC-SOD after single intravenous administration and its safety profile in healthy Chinese subjects. MATERIALS AND METHODS: This was a phase 1, randomized, double-blind, placebo-controlled, sequential, single-dose, and dose-escalation study. The study was done in 4 cohorts and a total of 40 subjects received a single dose of PC-SOD (from 20 to 160 mg). There were 12 subjects in each dose group (10 active treatments and 2 placebos), except a 20-mg group, in which all 4 subjects were given active treatment. Serial venous blood samples were collected up to 168 hours after dosing. Serum samples were analyzed using an enzyme-linked immunosorbent assay. Pharmacokinetic parameters of PC-SOD were calculated via noncompartmental analysis using the WinNonlin. RESULTS: After intravenous administration, PC-SOD reached the peak concentration quickly with a median tmax of 0.5 - 1.3 hours across all dose cohorts. After reaching Cmax, the mean T1/2 was 35.9 - 42.3 hours, which was independent of dose. The CL and Vz were 0.13 L/h and 6.72 L, 0.13 L/h and 7.33 L, and 0.11 L/h and 6.88 L for the 40, 80, and 160 mg dose cohorts, respectively. Over the dose range of 20 - 160 mg, the mean Cmax increased from 5,546.6 to 44,145.2 h×ng/mL and AUClast increased from 117,464.5 to 1,348,209.4 h×ng/mL. The 90% CI for ß of AUC or Cmax slightly exceeded the criterion, indicating that there was approximate dose proportionality over the range of 20 - 160 mg or 40 - 160 mg of PC-SOD. Generally, PC-SOD was well tolerated in doses up to 160 mg in healthy Chinese subjects. Reversible elevated blood triglyceride levels were reported in 2 subjects as moderate adverse events, and all other reported adverse events were considered to be mild. The possibility of a drug hypersensitivity syndrome was not high for PC-SOD in Chinese subjects based on current data. CONCLUSION: Single intravenous administrations of PC-SOD in doses up to 160 mg were well tolerated in healthy Chinese subjects. The prolonged half-life of PC-SOD was confirmed and independent of dose. Over the range of 20 - 160 mg, PC-SOD showed approximate dose proportionality. These findings suggest that it is worthwhile to investigate PC-SOD in clinical conditions characterized by a high radical overload.

[Optimization of preparation procedures of tanshinone-â ¡A /ß-cyclodextrin inclusion complex and dissolution study of tanshinone-â ¡A in vitro].

In this paper, tanshinone-ⅡA (Tan-IIA)/ß-cyclodextrin (ß-CD) inclusion complexes were prepared by saturated aqueous solution method. Based on the single factor experiment, Box-Benhnken design and response surface method were utilized to optimize the preparation procedures of tanshinone-ⅡA/ß-cyclodextrin inclusion complexes. The ratio of ß-CD to Tan-ⅡA, experimental temperature and time were defined as independent variables, while the yield of the inclusion complexes, encapsulation efficiency and the generalized "normalized value" were set as the response value. In addition, the inclusion complexes were characterized by infrared spectroscopy (IR) and nuclear magnetic resonance (NMR). The results showed that optimum preparation conditions for Tan-ⅡA/ß-CD inclusion complex were as follows: Tan-ⅡA/ß-CD ratio of 1:7, the temperature of 48 ℃ and the time of 3 h. Under the optimized conditions, the encapsulation efficiency of Tan-ⅡA/ß-CD inclusion complex was 84.75%. The Tan-IIA and ß-CD inclusion complex can significantly improve the dissolution of Tan-ⅡA.

[Chemical constituents, biological activities and quality control of plants from genus Pyrola].

Plants from the genus Pyrola are widely distributed in North Temperate zone. The quinones, phenol glycosides, terpenoids, flavonoids and volatile oil compounds have been identified from these plants. The in vivo and in vitro studies have shown that the genus Pyrola plants exhibit a wide range of pharmacological properties, including antioxidant, antitumor, antibacterial, anti-ischemia and anti-inflammatory activities. Based on analysis of the literature of the genus Pyrola plant, this review summarized the research on chemical constituents, pharmacology and quality control in recent years which can provide evidences for further investigation on the genus Pyrola plants.

The Blood-Brain Barrier Permeability of Lignans and Malabaricones from the Seeds of Myristica fragrans in the MDCK-pHaMDR Cell Monolayer Model.

The blood-brain barrier (BBB) permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg) were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (Papp) were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane-type and arylnaphthalene-type lignans showed poor to moderate permeabilities with Papp values at 10(-8)-10(-6) cm/s; those of 8-O-4'-neolignan and tetrahydrofuran-lignan were at 10(-6)-10(-5) cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their Papp values were at 10(-8)-10(-7) cm/s. To 5-methoxy-dehydrodiisoeugenol (2), erythro-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol acetate (6), verrucosin (8), and nectandrin B (9), an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1), myrislignan (7) and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg.

[Establishment of MDCK-pHaMDR cell model and standard operation procedure for assessing blood-brain barrier permeability of chemical components of traditional Chinese medicine].

To establish MDCK-pHaMDR cell model and standard operation procedure for assessing the blood-brain barrier permeability of chemical components of traditional Chinese medicine. MDCK-pHaMDR cell model was evaluated by determining the morphology features, transepithelial electrical resistance, bidirectional transport and intracellular accumulation of Rhodamine 123 and the apparent permeability of positive control drugs caffeine and atenolol. The MDCK-pHaMDR cell model had satisfactory integrity and tightness, and stable expression of P-gp. In addition, the transport results of the positive control drugs were consistent with the reported values in literature. All the parameters tested of the MDCK-pHaMDR cell model were consistent with the requirements, so the model can be used to study the blood-brain barrier permeability of chemical components of traditional Chinese medicine.

In vitro hypoglycemic effects of hot water extract from Auricularia polytricha (wood ear mushroom).

Viscous dietary fibers were shown to alleviate postprandial blood glucose. Auricularia polytricha (wood ear mushroom, WEM) contains rich amount fibers and water extract WEM was highly viscous. This study aimed to investigate whether WEM extract exhibited hypoglycemic effect in vitro. The effects of WEM extract on glucose adsorption, glucose diffusion, starch digestion and α-amylase activity were examined and compared to those of two high soluble fibers, psyllium and oat fiber and one insoluble fiber, cellulose. Our results showed that WEM extract and psyllium possessed similar ability to adsorb glucose which may thus decrease the level of dialysis glucose. The decrease of dialysis rate is dose-dependent. WEM extract can also suppress the activity of α-amylase which may thus inhibit the digestion of polysaccharides. Since WEM extract exhibited the ability to adsorb glucose and to suppress the activity of α-amylase; it might contribute a beneficial effect on postprandial levels of blood sugar.

[Establishment of Caco-2 cell monolayer model with collagen coating 6-well plates for study of traditional Chinese medicine prescription].

Caco-2 cell monolayer model is widely utilized in drug absorption study and 12-well transwellTM plates were commonly used to study the absorption of different kinds of natural products. To establish a stable method for the study of traditional Chinese medicine prescription, 6-well plates were chosen because of the larger well volumes than 12-well plates. To study the impacts of collagen kinds, coating density as well as coating time on the cell culture, the transepithelial electrical resistance of Caco-2 cell monolayers grown on different collagen coating transwells was determined, and the permeations of propranolol and atenolol as standard markers were detected with HPLC. The results showed that the kinds of collagen, the different coating densities and coating time of rat tail collagen had no significant influences on the Caco-2 cell monolayer integrality and absorption capacity. 6-well plates coated with 2 micro g Scm-2 rat tail collagen for 1 hour were enough reliable and suitable for the study of traditional Chinese medicine prescription in vitro.

An Analysis of Biopsychosocial Factors Associated With Chronic Pain Severity Among Hospitalized People Living With HIV in Shenzhen, China: A Cross-Sectional Study.

ABSTRACT: Chronic pain is a primary health problem in people living with HIV (PWH). However, there is limited research regarding chronic pain among PWH in Chinese health care settings. To investigate biopsychosocial factors of chronic pain severity, we conducted a cross-sectional study in Shenzhen, China. Chronic pain was defined as pain lasting for more than three months. Pain intensity was measured using the numeric rating scale (NRS). Among 123 hospitalized PWH, 78.86% of participants had mild pain and 21.14% had moderate-severe pain. Multiple logistic regression results indicated that PWH in moderate-severe pain group were more likely to have higher levels of interleukin [IL]-6 (OR = 1.034, 95% CI: 1.003-1.066, p = .029) and anxiety (OR = 1.334, 95% CI: 1.071-1.662, p = .010) than those in the mild chronic pain group. Targeted pain management interventions should be explored in clinical practices and future studies regarding PWH with high levels of IL-6 and anxiety.

Perinatal depression and infant and toddler neurodevelopment: A systematic review and meta-analysis.

Many studies have focused on the effect of perinatal depression on neurodevelopment among children and adolescents. However, only a few studies have explored this relationship in infants and toddlers with inconsistent results. We performed a systematic review and meta-analysis to evaluate the association between perinatal depression and infant and toddler neurodevelopment during the first two postnatal years. Twenty-three studies were included in this meta-analysis. Perinatal depression was associated with poorer cognitive (Cohen's d = -0.19, SE= 0.06, 95% CI = -0.30 to -0.08), language (Cohen's d = -0.24, SE = 0.09, 95% CI = -0.40 to -0.07), and motor (Cohen's d = -0.15, SE = 0.05, 95% CI = -0.26 to -0.05) development. Subgroup analyses showed that the types of maternal depression (prenatal depression vs. postnatal depression), the method of measuring maternal depression (rating scale vs. diagnostic interview), and the time interval between assessment of exposure and outcome had an impact on the observed effect about neurodevelopment of infants and toddlers. In addition, the results of our study pointed to a stronger significant association between prenatal depression and cognitive, language, and motor delays in infants and toddlers, whereas the association between postnatal depression and cognitive, language, and motor delays in infants and toddlers was not statistically significant. In conclusion, this study provided convincing evidence that the perinatal window is a sensitive period for offspring neurodevelopment.

Medicinal Value, Genetic Diversity, and Genetic Relationship Analysis of Auricularia cornea (Agaricomycetes) Based on ITS, ISSR, and SRAP Markers.

Wild resources of Auricularia cornea (A. polytricha) are abundant in China, and genetic diversity and genetic relationships analysis of A. cornea can provide basis for germplasm resource utilization and innovation and molecular marker-assisted breeding. In this study, 22 Auricularia strains collected were identified as A. cornea based on ITS sequence analysis, and its genetic diversity was examined by ISSR and SRAP markers. The results showed that a total of 415 bands were amplified by 11 selected ISSR primers, with an average amplification of 37.73 bands per primer, and the mean values of Ne, I, and H were 1.302, 0.368, and 0.219, respectively. A total of 450 bands were amplified by 10 SRAP primers, with an average of 45 bands per primer, and the average of Ne, I, and H were 1.263, 0.302, and 0.183, respectively. The unweighted pair-group method with arithmetic means analysis based on ISSR-SRAP marker data revealed that the genetic similarity coefficient between the tested strains was 0.73-0.97, and the strains could be divided into five groups at 0.742, which had a certain correlation with regional distribution. The results of PCOA and population structure analysis based on ISSR-SRAP data also produced similar results. These results demonstrate the genetic diversity and distinctness among wild A. cornea and provide a theoretical reference for the classification, breeding, germplasm innovation, utilization, and variety protection of A. cornea resources.

Alterations of the gut microbiota and fecal short-chain fatty acids in women undergoing assisted reproduction.

CONTEXT: The community structure of gut microbiota changes during pregnancy, which also affects the synthesis of short-chain fatty acids (SCFAs). However, the distribution of gut microbiota composition and metabolite SCFA levels are poorly understood in women undergoing assisted reproductive technology (ART). AIMS: To evaluate the changes in gut microbiota composition and metabolic SCFAs in women who received assisted reproduction treatment. METHODS: Sixty-three pregnant women with spontaneous pregnancy (SP) and nine with ART pregnancy were recruited to provide fecal samples. Gut microbiota abundance and SCFA levels were determined by 16S ribosomal RNA (rRNA) gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS). KEY RESULTS: The ART group showed decreased alpha diversity (the species richness or evenness in a sample). The principal coordinates analysis (a method of analysing beta diversity) showed significant difference in gut microbiota between the ART group versus the SP group (unweighted UniFrac distance, R 2 =0.04, P =0.003). Proteobacteria , Blautia and Escherichia-Shigella were enriched in the ART group, whereas the relative abundance of beneficial intestinal bacteria Faecalibacterium was lower than in the SP group. Different modes of conception were associated with several SCFAs (valeric acid (r =-0.280; P =0.017); isocaproic acid (r =-0.330; P =0.005); caproic acid (r =-0.336; P =0.004)). Significantly different SCFAs between the two groups were synchronously associated with the differential gut microbiota. CONCLUSIONS: The diversity and abundance of gut microbiota and the levels of SCFAs in women undergoing ART decreased. IMPLICATIONS: The application of ART shaped the microbial composition and metabolism, which may provide critical information for understanding the biological changes that occur in women with assisted reproduction.

Clathrin light chains negatively regulate plant immunity by hijacking the autophagy pathway.

The crosstalk between clathrin-mediated endocytosis (CME) and the autophagy pathway has been reported in mammals; however, the interconnection of CME with autophagy has not been established in plants. Here, we report that the Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopies Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants in both autoimmunity and nutrient sensitivity. Accordingly, the autophagy pathway is significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation, and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.