Improving drug-target affinity prediction via feature fusion and knowledge distillation.

Rapid and accurate prediction of drug-target affinity can accelerate and improve the drug discovery process. Recent studies show that deep learning models may have the potential to provide fast and accurate drug-target affinity prediction. However, the existing deep learning models still have their own disadvantages that make it difficult to complete the task satisfactorily. Complex-based models rely heavily on the time-consuming docking process, and complex-free models lacks interpretability. In this study, we introduced a novel knowledge-distillation insights drug-target affinity prediction model with feature fusion inputs to make fast, accurate and explainable predictions. We benchmarked the model on public affinity prediction and virtual screening dataset. The results show that it outperformed previous state-of-the-art models and achieved comparable performance to previous complex-based models. Finally, we study the interpretability of this model through visualization and find it can provide meaningful explanations for pairwise interaction. We believe this model can further improve the drug-target affinity prediction for its higher accuracy and reliable interpretability.

Effects of Citrobacter freundii on sturgeon: Insights from skin mucosal immunology and microbiota.

Skin mucus analysis has recently been used as a non-invasive method to evaluate for fish welfare. The present research study was conducted to examine the skin mucosal immunity and skin microbiota profiles of sturgeons infected with Citrobacter freundii. Our histology results showed that the thickness of the epidermal layer of skin remained thinner, and the number of mucous cells was significantly decreased in sturgeons after infection (p < 0.05). Total protein, alanine aminotransferase, aspartate aminotransferase, superoxide dismutase, and creatine kinase levels in the mucus showed biphasic pattern (decrease and then increase). Lactate dehydrogenase, lysozyme, and acid phosphatase activities in the mucus showed an increasing trend after infection. Furthermore, 16S rRNA sequencing also revealed that C. freundii infection also affected the diversity and community structure of the skin mucus microbiota. An increase in microbial diversity (p > 0.05) and a decrease in microbial abundance (p < 0.05) after infection were noted. The predominant bacterial phyla in the skin mucus were Proteobacteria, Fusobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Specifically, the relative abundance of Fusobacteria increased after infection. The predominant bacterial genera in the skin mucus were Cetobacterium, Pelomonas, Bradyrhizobium, Flavobacterium, and Pseudomonas. The relative abundance of Cetobacterium, Pseudomonas, and Flavobacterium increased after infection. Our current research findings will provide new insights into the theoretical basis for future research studies exploring the mechanism of sturgeon infection with C. freundii.

Theoretical Studies on Selectivity of HPK1/JAK1 Inhibitors by Molecular Dynamics Simulations and Free Energy Calculations.

Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T cell receptor, which has been regarded as a potential target for immunotherapy. Yu et al. observed the off-target effect of the high-throughput screening HPK1 kinase inhibitor hits on JAK1 kinase. The off-target effect is usually due to the lack of specificity of the drug, resulting in toxic side effects. Therefore, exploring the mechanisms to selectively inhibit HPK1 is critical for developing effective and safe inhibitors. In this study, two indazole compounds as HPK1 inhibitors with different selectivity towards JAK1 were used to investigate the selectivity mechanism using multiple computational methods, including conventional molecular dynamics simulations, binding free energy calculations and umbrella sampling simulations. The results indicate that the salt bridge between the inhibitor and residue Asp101 of HPK1 favors their selectivity towards HPK1 over JAK1. Information obtained from this study can be used to discover and design more potent and selective HPK1 inhibitors for immunotherapy.

A common polymorphism decreases LRP1 mRNA stability and is associated with increased plasma factor VIII levels.

The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups. However, while analyzing the association between the eight SNPs and plasma FVIII levels, subjects with T/T genotype of rs1800137 (vs. CC+CT) were found to be associated with higher FVIII levels (23.5IU/dL; 95% confidence interval, 7.4-39.5IU/dL; P=0.0044) after adjusting for age, gender, estimated glomerular filtration rate, O blood type, inflammatory state, and body mass index. An analysis of the mRNA stability and abundance was designed and performed using minigene system transfected into HepG2 cells to assess the possible differences in mRNA stabilities between rs1800137 CC (rs1800137C) and TT (rs1800137T) genotypes. Site-directed mutagenesis revealed that rs1800137T accounts for the observed decrease in mRNA stability. The SNP rs1800137, located in exon 8, has been identified as an exon-splicing enhancer in silico. However, alternative splicing of LRP1 without inclusion of exon 8 was not identified. In transfected HepG2 cells, cycloheximide slowed down the degradation of the rs1800137T-containing minigene. These results demonstrate that synonymous SNP rs1800137 can lead to increased plasma FVIII levels due to decreased mRNA stability via translation-dependent mRNA degradation associated with codon optimality.

cDNA isolation and functional characterization of squalene synthase gene from Ornithogalum caudatum.

As the first step of ongoing efforts to investigate the genes responsible for the biosynthesis of steroidal saponins in the medicinal plant Ornithogalum caudatum, this investigation reported the cDNA isolation, prokaryotic expression and functional characterization of squalene synthase (SQS) gene from O. caudatum for the first time. Specifically, two unigenes showing high sequence identity to SQS were retrieved from RNA-Taq data, and then a full-length OcSQS1 corresponding to the two unigenes was isolated from O. caudatum genome by a nested PCR assay. The open reading frame of OcSQS1 was 1230 bp and encoded a polypeptide of 409 aa. OcSQS1 was predicted to be a membrane-bound protein with at least four conserved motifs associated with binding, regulatory and catalytic activities of OcSQS1 and two transmembrane domains. Next, many attempts to generate soluble OcSQS1 in heterologous Escherichia coli were made, including optimization of expression conditions, application of varied expression plasmids with different tags, secretory peptides and molecular chaperones, and truncated mutation of OcSQS1. Finally, the successful availability of a soluble, truncated OcSQS1 mutant was achieved by combinational use of the utensils from the vast genetic toolbook. Moreover, this truncated OcSQS1 mutant retained the folding capability as well as its catalytic activity, converting FPP to form squalene. Importantly, the present research tentatively verified the involvement of the second transmembrane domain in the proper folding of the recombinant OcSQS1 protein.

Crystal Structures of Two New Gold-Copper Bimetallic Nanoclusters: CuxAu25-x(PPh3)10(PhC2H4S)5Cl22+ and Cu3Au34(PPh3)13(tBuPhCH2S)6S23.

Herein, we report the synthesis and atomic structures of the cluster-assembled CuxAu25-x(PPh3)10(PhCH2CH2S)5Cl22+ and Cu3Au34(PPh3)13(tBuPhCH2S)6S23+ nanoclusters (NCs). The atomic structures of both NCs were precisely determined by single-crystal X-ray crystallography. The CuxAu25-x(PPh3)10(PhC2H4S)5Cl22+ NC was assembled by two icosahedral M13 via a vertex-sharing mode. The Cu atom partially occupies the top and waist sites and is monocoordinated with chlorine or thiol ligands. Meanwhile, the Cu3Au34(PPh3)13(tBuPhCH2S)6S23+ NC can be described as three 13-atom icosahedra sharing three vertexes in a cyclic fashion. The three Cu atoms all occupy the internal positions of the cluster core. What is more important is that all three Cu atoms in Cu3Au34 are monocoordinated by the bare S atoms. The absorption spectra of the as-synthesized bimetallic NCs reveal that the additional metal doping and different cluster assemblies affect the electronic structure of the monometallic NCs.

Transcriptome-enabled discovery and functional characterization of enzymes related to (2S)-pinocembrin biosynthesis from Ornithogalum caudatum and their application for metabolic engineering.

BACKGROUND: (2S)-Pinocembrin is a chiral flavanone with versatile pharmacological and biological activities. Its health-promoting effects have spurred on research effects on the microbial production of (2S)-pinocembrin. However, an often-overlooked salient feature in the analysis of microbial (2S)-pinocembrin is its chirality. RESULTS: Here, we presented a full characterization of absolute configuration of microbial (2S)-pinocembrin from engineered Escherichia coli. Specifically, a transcriptome-wide search for genes related to (2S)-pinocembrin biosynthesis from Ornithogalum caudatum, a plant rich in flavonoids, was first performed in the present study. A total of 104,180 unigenes were finally generated with an average length of 520 bp. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping assigned 26 unigenes, representing three enzyme families of 4-coumarate:coenzyme A ligase (4CL), chalcone synthase (CHS) and chalcone isomerase(CHI), onto (2S)-pinocembrin biosynthetic pathway. A total of seven, three and one full-length candidates encoding 4CL, CHS and CHI were then verified by reverse transcription polymerase chain reaction, respectively. These candidates were screened by functional expression in E. coli individual or coupled multienzyme reaction systems based on metabolic engineering processes. Oc4CL1, OcCHS2 and OcCHI were identified to be bona fide genes encoding respective pathway enzymes of (2S)-pinocembrin biosynthesis. Then Oc4CL1, OcCHS2 and MsCHI from Medicago sativa, assembled as artificial gene clusters in different organizations, were used for fermentation production of (2S)-pinocembrin in E. coli. The absolute configuration of the resulting microbial pinocembrin at C-2 was assigned to be 2S-configured by combination of retention time, UV spectrum, LC-MS, NMR, optical rotation and circular dichroism spectroscopy. Improvement of (2S)-pinocembrin titres was then achieved by optimization of gene organizations, using of codon-optimized pathway enzymes and addition of cerulenin for increasing intracellular malonyl CoA pools. Overall, the optimized strain can produce (2S)-pinocembrin of 36.92 ± 4.1 mg/L. CONCLUSIONS: High titre of (2S)-pinocembrin can be obtained from engineered E. coli by an efficient method. The fermentative production of microbial (2S)-pinocembrin in E. coli paved the way for yield improvement and further pharmacological testing.

Preparation of sequence-controlled triblock copolymer-grafted silica microparticles by sequential-ATRP for highly efficient glycopeptides enrichment.

As one of the most important subproteomes in eukaryote cells, N-glycoproteins play crucial roles in various of biological processes and have long been considered closely correlated with the occurrence, progression, and metastasis of cancer. Comprehensive characterization of protein N-glycosylation and association of their aberrant patterns to the corresponding cancer stage may provide a unique way to discover new diagnostic biomarkers and therapeutic drug targets. However, the extremely complex nature of biological samples and relatively low abundance of N-glycosylated proteins makes the enrichment of glycoprotein/glycopeptide a prerequisite for large scale N-glycosylation identification. In this work, we prepared sequence controlled triblock copolymer grafted silica-microparticles (TCP-SMs) by sequential atom transfer radical polymerization (sequential-ATRP) of monosaccharides and zwitterionic-ion monomers for highly efficient and selective glycopeptides enrichment. The triblock copolymer is composed of sequence defined poly zwitterionic-ion, poly-N-acetylglucosamine and poly mannose blocks. The glycopolymer blocks carrying densely packed pendent sugars are excellent mimics of the natural carbohydrate clusters and may induce multivalent carbohydrate-carbohydrate interaction (CCI) with the target glycopeptides. Therefore, increased retention of glycopeptides can be expected by the combination of CCI and zwitterionic-HILIC interaction. As a result, 1244 glycopeptides were identified after TCP-SMs enrichment from mouse liver, which are 65-120% higher than that obtained by homoglycopolymer or random-copolymer grafted silica microparticles prepared using the conventional free radical polymerization. These results demonstrate the critical role of sequence-defined block copolymer of TCP-SMs for obtaining enhanced affinity toward glycopeptides and the potential of this sequential-ATRP strategy to integrate different affinity moieties into one enrichment material to achieve deeper coverage in protein PTM mapping.

Shortened Activated Partial Thromboplastin Time Is Associated With Acute Ischemic Stroke, Stroke Severity, and Neurological Worsening.

BACKGROUND: The role played by hemostasis in the pathogenesis of ischemic strokes is still controversial. The activated partial thromboplastin time (APTT) measures the time necessary to generate fibrin from initiation of the intrinsic pathway. In the present study, we looked for a possible association of ischemic strokes with the shortened APTT. METHODS: The study population consisted of 154 patients with acute ischemic strokes who had been admitted from December 2013 to December 2014 to the Department of Neurology, Chiayi Chang Gung Memorial Hospital, and 71 control subjects with no history of stroke. RESULTS: In a univariate risk analysis, shortened APTT was associated with an odds ratio (OR) for acute ischemic strokes of up to 1.86 (95% confidence interval [CI], 1.06-3.29, P = .031). In a multivariate analysis using a logistic regression model including age, sex, hypertension, diabetes mellitus, and shortened APTT, shortened APTT was still found to significantly add to the risk of ischemic stroke (OR = 2.12 with 95% CI, 1.13-3.98, P = .020). Shortened APTT was also associated significantly with neurological worsening (OR = 3.72 with 95% CI 1.03-13.5, P = .046). As for stroke severity, shortened APTT was associated with an OR for moderate/severe stroke of up to 3.42 (95% CI, 1.53-7.61, P = .003). CONCLUSION: Shortened APTT is a prevalent and independent risk factor for ischemic stroke, stroke severity, and neurological worsening after acute stroke.

Dual matrix-based immobilized trypsin for complementary proteolytic digestion and fast proteomics analysis with higher protein sequence coverage.

In an age of whole-genome analysis, the mass spectrometry-based bottom-up strategy is now considered to be the most powerful method for in-depth proteomics analysis. As part of this strategy, highly efficient and complete proteolytic digestion of proteins into peptides is crucial for successful proteome profiling with deep coverage. To achieve this goal, prolonged digestion time and the use of multiple proteases have been adopted. The long digestion time required and tedious sample treatment steps severely limit the sample processing throughput. Though utilization of immobilized protease greatly reduces the digestion time, highly efficient proteolysis of extremely complex proteomic samples remains a challenging task. Here, we propose a dual matrix-based complementary digestion method using two types of immobilized trypsin with opposite matrix hydrophobicity prepared by attaching trypsin on hydrophobic or hydrophilic polymer-brush-modified nanoparticles. The polymer brushes on the nanoparticles serve as three-dimensional supports for a large amount of trypsin immobilization and lead to ultrafast and highly efficient protein digestion. More importantly, the two types of immobilized trypsin show high complementarity in protein digestion with only ∼60% overlap in peptide identification for yeast and membrane protein of mouse liver. Complementary digestion by applying these two types of immobilized trypsin together leads to obviously enhanced protein and peptide identification. Furthermore, the dual matrix-based complementary digestion shows particular advantage in the digestion of membrane proteins, as twice the number of identified peptides is obtained compared with solution digestion using free proteases, demonstrating its potential as a promising alternative to promote proteomics analysis with higher protein sequence coverage.

Differential adhesion and actomyosin cable collaborate to drive Echinoid-mediated cell sorting.

Cell sorting involves the segregation of two cell populations into `immiscible' adjacent tissues with smooth borders. Echinoid (Ed), a nectin ortholog, is an adherens junction protein in Drosophila, and cells mutant for ed sort out from the surrounding wild-type cells. However, it remains unknown which factors trigger cell sorting. Here, we dissect the sequence of this process and find that cell sorting occurs when differential expression of Ed triggers the assembly of actomyosin cable. Conversely, Ed-mediated cell sorting can be rescued by recruitment of Ed, via homophilic or heterophilic interactions, to the wild-type cell side of the clonal interface, even when differential Ed expression persists. We found, unexpectedly, that when actomyosin cable was largely absent, differential adhesion was sufficient to cause limited cell segregation but with a jagged tissue border (imperfect sorting). We propose that Ed-mediated cell sorting is driven both by differential Ed adhesion that induces cell segregation with a jagged border and by actomyosin cable assembly at the interface that smoothens this border.

Relationship between serum uric acid and sarcopenia in geriatric heart failure patients with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) presents a serious risk to human health. The increased prevalence of sarcopenia in the HFpEF population has a negative impact on patient prognosis. Uric acid (UA) is the byproduct of purine metabolism and is harmful to the cardiovascular system. This study aims to establish the potential relationship between sarcopenia and serum UA in HFpEF patients. METHODS: Data were obtained from 180 individuals (aged ≥60 years) with HFpEF admitted to the Geriatric Department of Jiangsu Province Hospital between January 2021 and December 2022. The UA values were grouped into 4 quartiles (Q1-Q4). Logistic generalized linear models and restricted cubic spline (RCS) regression were used to analyze the relationship between sarcopenia and UA. Subgroups based on gender were utilised for further analysis. RESULTS: After adjusting for covariates, odds ratios (ORs) and 95 % confidence intervals (CIs) for sarcopenia prevalence in the 2nd, 3rd, and 4th quartiles were 2.56 (0.57-12.65), 4.94 (1.10-24.49), and 6.95 (1.30-44.25), respectively, unlike the 1st quartile (P for trend = 0.022). The RCS plot demonstrated a positive linear relationship between serum UA levels and sarcopenia (P for non-linearity = 0.190). A sex-based subgroup analysis revealed a statistically significant relationship between UA and sarcopenia in males (P < 0.05). CONCLUSIONS: In summary, the prevalence of sarcopenia is positively related to serum UA levels among the elderly diagnosed with HFpEF. Due to the cross-sectional nature of the study design, additional investigations are necessary to validate our findings and identify the optimal range for UA reduction.

Perfluorooctanoate and nano titanium dioxide impair the byssus performance of the mussel Mytilus coruscus.

Perfluorooctanoate (PFOA) is widely used as a surfactant and has metabolic, immunologic, developmental, and genetic toxicity on marine organisms. However, the effects of PFOA on individual defense functions in mussels in the presence of titanium dioxide nanoparticles (nano-TiO2) are poorly understood. To investigate the defense strategies and regulatory mechanisms of mussels under combined stressors, the thick-shell mussels Mytilus coruscus were exposed to different PFOA concentrations (0, 2 and 200 µg/L) and nano-TiO2 (0 and 0.1 mg /L, size: 25 nm) for 14 days. The results showed that, compared to the control group, PFOA and nano-TiO2 significantly reduced the number of byssal threads (NBT), byssal threads length (BTL), diameter of proximal threads (DPB), diameter of middle threads (DMB), diameter of distal byssal threads (DDB), adhesive plaque area (BPA), and breaking force of byssal threads (N). Under the influence of PFOA and nano-TiO2, the morphological surface smoothness of the fractured byssal threads surface increased, concurrently inducing an increased surface roughness in the adhesive plaques. Additionally, under the presence of PFOA and nano-TiO2, the foot displayed dispersed tissue organization and damaged villi, accompanied by an increased incidence of cellular apoptosis and an upregulation of the apoptosis gene caspase-8. Expression of the adhesion gene mfp-3 and byssal threads strength genes (preCOL-D, preCOL-NG) was upregulated. An interactive effect on the performance of byssal threads is observed under the combined influence of PFOA and nano-TiO2. Under co-exposure to PFOA and nano-TiO2, the performance of the byssal threads deteriorates, the foot structure is impaired, and the genes mRNA expression of byssal thread secretory proteins have compensated for the adhesion and byssal threads strength by up-regulation. Within marine ecosystems, organic and particulate contaminants exert a pronounced effect on the essential life processes of individual organisms, thereby jeopardizing their ecological niche within community assemblages and perturbing the dynamic equilibrium of the overarching ecosystem. ENVIRONMENTAL IMPLICATION: Perfluorooctanoic acid (PFOA) is prone to accumulate in marine organisms. TiO2 nanoparticles (nano-TiO2) are emerging environmental pollutants frequently found in marine environment. The effects of PFOA and nano-TiO2 on marine mussels are not well understood, and their toxic mechanisms remain largely unknown. We investigated the impacts of PFOA and nano-TiO2 on mussel byssus defense mechanisms. By assessing byssus performance indicators, morphological structures of the byssus, subcellular localization, and changes in byssal secretion-related genes, we revealed the combined effects and mechanisms through which these two types of pollutants may affect the functional capabilities and survival of mussels in the complex marine ecosystem.

Modified enzyme-linked immunosorbent assay strategy using graphene oxide sheets and gold nanoparticles functionalized with different antibody types.

Gold nanoparticles (GNPs) and graphene oxide (GO) sheets are excellent nano carriers in many analytical methods. In this study, a modified enzyme-linked immunosorbent assay (ELISA) strategy was developed using antibody-functionalized GO sheets and GNPs. This modification significantly reduced the limit of detection (LOD) and cost greatly of this assay. The applicability of the method was demonstrated by detecting HSP70 in a human serum sample. This result suggests that the 3G-ELISA method is feasible to detect an antigen in a complex mixture, and the LOD is up to 64-fold and the cost is as low as one-tenth of the conventional ELISA method.

Early Neurocognitive Function With Propofol or Desflurane Anesthesia After Laser Laryngeal Surgery With Low Inspired Oxygen.

PURPOSE: The effects of general anesthetics on cognitive impairment are unclear and complicated. Laser laryngeal surgery (LLS) requires the administration of low levels of oxygen, which may increase the risk of desaturation and brain function impairment. This prospective randomized trial aimed to compare the effects of desflurane and propofol-based general anesthesia on the occurrence of early postoperative cognitive decline in elderly patients undergoing LLS. METHODS: Seventy-three patients classified as American Society of Anesthesiologists grade I or II and at least 65 years of age were randomly allocated to receive either desflurane-based (Group D) or propofol-based (Group P) anesthesia during LLS. The standard anesthesia protocol was performed, with a bispectral index between 40 and 60 and a mean arterial pressure within 20% of baseline values. Intraoperative regional oxygen saturation values were recorded. Each patient was assessed using the mini-mental state examination (MMSE) test during the preoperative period (baseline), 30 min after extubation in the postanesthesia care unit, and 1, 3, and 24 h after surgery. RESULTS: MMSE scores improved slightly in both groups compared to baseline during the early postoperative period, but these increases were not statistically significant. No significant differences were identified in MMSE scores between groups. Only three patients (9.6%) in group D and one patient (3.1%) in group P developed cognitive impairment (p = 0.583). CONCLUSION: Low intraoperative inspired oxygen concentration during short-duration LLS did not reduce early postoperative cognitive function in elderly patients. Desflurane or propofol-based anesthesia had similar effects on early neurocognition after LLS. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:640-646, 2023.

Association of urinary thallium with hypertension in children and adolescents aged 8-17 years: NHANES 2005-2018.

Hypertension is a key risk factor for cardiovascular disease (CVD). Thallium is a highly toxic metal that exists in all aspects of our lives and can cause damage to human health. The aim of this study was to identify the potential correlation between urinary thallium (U-Tl) and hypertension in American youth aged 8-17 years. The National Health and Nutritional Examination Survey (NHANES) database was mined for cross-sectional information on 2295 American children and adolescents aged 8-17 years. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to measure U-Tl levels, and the results were categorized into four quartiles (Q1-Q4). Logistic generalized linear models and unweighted restricted cubic spline (RCS) regression were used to investigate the relationship between U-Tl and hypertension. After adjusting for covariates, the odds ratios (ORs) at 95% confidence intervals (CIs) for hypertension prevalence in the 2nd, 3rd, and 4th quartiles were 0.43 (0.22-0.81), 0.54 (0.29-0.99), and 0.43 (0.22-0.81), when compared to the lowest quartile (P for trend = 0.024). RCS plot showed a negative linear correlation between log2-transformed U-Tl levels and hypertension (P for non-linearity = 0.869). Subgroup analysis based on sex indicated a statistically significant link between U-Tl and hypertension in male (P < 0.05). There is a negative linear relationship between U-Tl and hypertension in American children and adolescents aged 8-17 years with low thallium exposure. Due to the nature of cross-sectional studies, further studies are necessary to validate our conclusions and elucidate possible mechanisms.

Practice of pharmaceutical services and prescription analysis in internet-based psychiatric hospitals during COVID-19 pandemic in Wuxi, China.

Objective: To study the practice of pharmaceutical services in internet-based psychiatric hospitals, and to analyze the prescriptions to ensure the safety and efficacy of internet-based medication in Wuxi, China. Methods: All 1,259 internet-based prescriptions from our hospital in 2022 were collected, and data on patients' age, gender, diagnosis, medications used, medication types, dosage forms, rationality of medication use, and reasons for irrationality were analyzed through descriptive statistics. Results: In the electronic prescriptions of internet-based psychiatric hospitals, females accounted for the majority (64.50%), with a female-to-male ratio of 1.82:1. Middle-aged and young adults accounted for the majority of patients (57.50%). There were 47 diagnosed diseases involved, with 89 types of medications used and 1,938prescriptions issued. Among them, there were 78 types of western medicine with 1,876 prescriptions (96.80%), and 11 types of traditional Chinese medicine with 62 prescriptions (3.20%). The main medications used were anti-anxiety and antidepressant medications (44.94%) and psychiatric medications (42.21%). The dosage forms were all oral, with tablets (78.53%), capsules (17.54%), and solution preparations (2.17%) being the top three in frequency. According to the prescription review results, the initial pass rate of internet-based system review was 64.26%. After intervention by the internet-based system and manual review by pharmacist reviewers, the final pass rate of internet-based prescriptions reached 99.76%. Conclusion: The practice of pharmaceutical services and prescription analysis in internet-based psychiatric hospitals could significantly improve medication rationality, which fills the research gap in this field. In addition, it promotes the transformation of pharmaceutical service models.

Evaluation of clinical relevance and underlying pathology for hemodynamic compromise in acute small subcortical infarction using MRI-based neuroimaging markers.

BACKGROUND: Hemodynamic compromise has been observed in patients with acute small subcortical infarction (SSI), and it may play a critical role in the development of early neurological deterioration (END). This study aimed to evaluate the clinical relevance and underlying pathology of hemodynamic compromise in SSI using MRI-based neuroimaging markers. METHODS: We retrospectively analyzed data and imaging of previous prospective studies. Patients with acute SSI in penetrating artery territories were recruited, all of whom underwent perfusion MRI within 24 h of stroke onset. We examined the relationships among perfusion defects and neuroimaging markers of small vessel disease, including white matter hyperintensities, cerebral microbleeds, enlarged perivascular spaces (EPVSs) and lacunes. RESULTS: One hundred and seven patients were recruited, of whom 21 (19.6%) had END and 55 (51.4%) had visible perfusion defects. Patients with perfusion defects were associated with a higher rate of END (34.5% vs. 3.8%; p < 0.001), higher initial National Institutes of Health Stroke Scale scores (5.4 vs. 3.4, p < 0.001), higher rate of branch atheromatous disease (61.8% vs. 34.6%, p = 0.005) and higher rate of poor outcome at 3 months (40.0% vs. 5.4%; p = 0.005). In multiple logistic regression, perfusion defects were significantly associated with basal ganglia EPVS scores (adjusted odds ratio [aOR]: 3.93; 95% confidence interval [CI]: 1.76-8.77; p = 0.001) and branch atheromatous disease (aOR: 2.64; 95% CI: 1.06-6.60; p = 0.037). CONCLUSION: Hemodynamic compromise in acute SSI was highly related to the development of END, basal ganglia EPVS and branch atheromatous disease, suggesting the correlation with underlying pathologies of hypertensive arteriopathy and atherosclerosis.

Response of moulting genes and gut microbiome to nano-plastics and copper in juvenile horseshoe crab Tachypleus tridentatus.

Nanoplastics (NPs) and heavy metals are typical marine pollutants, affecting the gut microbiota composition and molting rate of marine organisms. Currently, there is a lack of research on the toxicological effects of combined exposure to horseshoe crabs. In this study, we investigated the effects of NPs and copper on the expression of molt-related genes and gut microbiome in juvenile tri-spine horseshoe crabs Tachypleus tridentatus by exposing them to NPs (100 nm, 104 particles L-1) and/or Cu2+ (10 µgL-1) in seawater for 21 days. Compared with the control group, the relative mRNA expression of ecdysone receptor (EcR), retinoid x receptor (RXR), calmodulin-A-like isoform X1 (CaM X1), and heat shock 70 kDa protein (Hsp70) were significantly increased under the combined stress of NPs and Cu2+. There were no significant differences in the diversity and abundance indices of the gut microbial population of horseshoe crabs between the NPs and/or Cu2+ groups and the control group. According to linear discriminant analysis, Oleobacillus was the most abundant microorganism in the NPs and Cu2+ stress groups. These results indicate that exposure to either NPs stress alone or combined NPs and Cu2+ stress can promote the expression levels of juvenile molting genes. NPs exposure has a greater impact on the gut microbial community structure of juvenile horseshoe crabs compared to Cu2+ exposure. This study is helpful for predicting the growth and development of horseshoe crabs under complex environmental pollution.

Study on the Collection Efficiency of Bioaerosol Nanoparticles by Andersen-Type Impactors.

Airborne transmission is much more common than previously thought. Based on our knowledge about SARS-COV-2 (COVID-19) infection, the aerosol transmission routes for all respiratory infections must be reassessed. Thus far, the COVID-19 outbreak has caused catastrophic public health and economic crises, posing a serious threat to the lives and health of people around the world and directing public attention toward the airborne transmission of pathogens. The novel coronavirus transmission in the form of nanoaerosols in a wider range hinders prevention and early warning efforts. As a classical bioaerosol sampler, the Andersen six-stage sampler is widely used in the collection and research of aerosol particles. In this study, the physical and biological collection efficiency of the six-stage sampler was explored by qPCR and colony counting method. Results showed that the physical collection efficiency reached more than 50% when the particle size was larger than 0.75 µm. However, the overall biological collection efficiency was only 0.25%. In addition, fluorescence microscopy and flow cytometry were used to detect the microbial state after sampling, and the results showed that the proportion of the collected live bacteria was less than 15% of the total. This result is of great significance not only for the application of the Andersen six-stage sampler in collecting nanosized bioaerosols, but also provides reference for the selection of subsequent detection technologies for effective collection.