ABSTRACT
BACKGROUND: Many studies have shown that the COVID-19 pandemic has increased the risk of suicidal tendencies among the public. However, there is limited research reporting on the changing trends in suicidal ideation after 2020 in the context of the long-term normalization of COVID-19 prevention and control measures in China. METHODS: The self-administered online questionnaire was adopted to collect 12-month suicidal ideation, depressive symptoms, anxiety symptoms, stress, and some demographic information from university students by convenient cluster sampling in Shandong, Shaanxi, and Jilin Provinces, China. Multivariate logistic regressions were performed to assess the association between different factors and suicidal ideation. RESULTS: The prevalence of 12-month suicidal ideation from 2021 to 2023 among university students was 3.89â¯%, 5.81â¯%, and 4.33â¯%, respectively, showing a trend of first increasing and then decreasing. The trends presented a similar tendency in the subgroups according to gender, majors, and grades, except among urban freshman-year students. The associated factors of suicidal ideation were different among university students in different surveys. However, female gender, poor mental health, and depressive symptoms were linked to a higher risk of suicidal ideation. LIMITATIONS: More representative large-scale longitudinal studies should be used to monitor the suicidal behavior of university students. CONCLUSIONS: The prevalence of 12-month suicidal ideation among Chinese university students exhibited a pattern of initial increase followed by a subsequent decrease from 2021 to 2023. Despite the complete lifting of COVID-19 prevention and control measures in China, the prolonged three-year epidemic may have enduring adverse effects on university students, underscoring the ongoing importance of providing continuous mental health services to this population.
ABSTRACT
Making silage is a green process to use the fast-growing water hyacinth (Eichhornia crassipes) biomass. However, the high moisture (â¼95%) of the water hyacinth is the biggest challenge to making silage while its effects on fermentation processes are less studied. In this study, water hyacinths silage with different initial moistures were conducted to investigate the fermentation microbial communities and their roles on the silage qualities. Results show that both silages with 70% (S70) and 90% (S90) of initial moistures achieved the target of silage fermentation, however, their microbial processes were significantly different. Their succession directions of microbial communities were different: Plant cells in S70 were destroyed by the air-dry treatment, thus there were more soluble carbohydrates, which helped the inoculated fermentative bacteria become dominant (Lactobacillus spp. > 69%) and produce abundant lactic acid; In contrast, stochastic succession became dominant over time in S90 (NST = 0.79), in which Lactobacillus spp. and Clostridium spp. produced butyric that also obviously decreased the pH and promoted the fermentation process. Different microbial succession led to different metabolic patterns: S70 had stronger starch and sucrose metabolisms while S90 had stronger amino acid and nitrogen metabolisms. Consequently, S70 had higher lactic acid, crude protein and lower ammonia nitrogen and S90 had higher in vitro digestibility of dry matter and higher relative feeding value. Moreover, the variance partitioning analysis indicated that moisture could only explain less information (5.9%) of the microbial assemblage than pH value (41.4%). Therefore, the colonization of acid-producing bacteria and establishment of acidic environment were suggested as the key on the silage fermentation no matter how much is the initial moisture. This work can provide a basis for the future preparation of high-moisture raw biomasses for silage.
Subject(s)
Eichhornia , Silage , Silage/analysis , Silage/microbiology , Lactobacillus/metabolism , Lactic Acid/metabolism , Bacteria/metabolism , Fermentation , Nitrogen/analysisABSTRACT
BACKGROUND AND AIM: To explore the possible mechanism of Dachaihu Decoction (DCHD) in the treatment of AP, and use in vivo experiments to verify. METHODS: The targets and active ingredients of DCHD in the treatment of AP were obtained through network pharmacology, and the preliminary verification was carried out by molecular docking. Caerulein was used to develop the AP rat model. H&E staining was performed to observe variations in pancreatic tissue. Western blot and RT-qPCR were conducted to evaluate the associated proteins and mRNA. RESULTS: The network pharmacology and molecular docking results showed that the key targets (EGFR, TNF, SRC, VEGFA and CTNNB1) and key active components (beta-sitosterol, stigmasterol, baicalein, quercetin, and kaempferol) of DCHD in the treatment of AP had good binding. H&E staining revealed that rat pancreatic tissues considerably damaged post caerulein intervention, and it has also been suggested that DCHD ameliorates damage to pancreatic tissue. Simultaneously, EGFR, TNF, SRC, VEGFA protein, and mRNA expression levels were increased in the model group compared to the blank group (P < 0.01), whereas CTNNB1 expression was found to be decreased in the model group (P < 0.01). Compared with the model group, the protein expression levels of EGFR, TNF, SRC, and VEGFA in the treatment group were down-regulated (P < 0.01), and CTNNB1 was up-regulated (P < 0.05). CONCLUSION: DCHD protects pancreatic tissues and improves symptoms in AP rats by upregulating CTNNB1 protein and mRNA while inhibiting EGFR, TNF, SRC, and VEGFA protein and mRNA expression.
Subject(s)
Drugs, Chinese Herbal , Pancreatitis , Rats , Animals , Pancreatitis/drug therapy , Pancreatitis/metabolism , Molecular Docking Simulation , Artificial Intelligence , Ceruletide/therapeutic use , Acute Disease , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/chemistry , RNA, Messenger/genetics , RNA, Messenger/metabolism , ErbB ReceptorsABSTRACT
Modeling the joint distribution of high-dimensional data is a central task in unsupervised machine learning. In recent years, many interests have been attracted to developing learning models based on tensor networks, which have the advantages of a principle understanding of the expressive power using entanglement properties, and as a bridge connecting classical computation and quantum computation. Despite the great potential, however, existing tensor network models for unsupervised machine learning only work as a proof of principle, as their performance is much worse than the standard models such as restricted Boltzmann machines and neural networks. In this Letter, we present autoregressive matrix product states (AMPS), a tensor network model combining matrix product states from quantum many-body physics and autoregressive modeling from machine learning. Our model enjoys the exact calculation of normalized probability and unbiased sampling. We demonstrate the performance of our model using two applications, generative modeling on synthetic and real-world data, and reinforcement learning in statistical physics. Using extensive numerical experiments, we show that the proposed model significantly outperforms the existing tensor network models and the restricted Boltzmann machines, and is competitive with state-of-the-art neural network models.
ABSTRACT
Alkanes are widespread in the ocean, and Alcanivorax is one of the most ubiquitous alkane-degrading bacteria in the marine ecosystem. Small RNAs (sRNAs) are usually at the heart of regulatory pathways, but sRNA-mediated alkane metabolic adaptability still remains largely unknown due to the difficulties of identification. Here, differential RNA sequencing (dRNA-seq) modified with a size selection (~50-nt to 500-nt) strategy was used to generate high-resolution sRNAs profiling in the model species Alcanivorax dieselolei B-5 under alkane (n-hexadecane) and non-alkane (acetate) conditions. As a result, we identified 549 sRNA candidates at single-nucleotide resolution of 5'-ends, 63.4% of which are with transcription start sites (TSSs), and 36.6% of which are with processing sites (PSSs) at the 5'-ends. These sRNAs originate from almost any location in the genome, regardless of intragenic (65.8%), antisense (20.6%) and intergenic (6.2%) regions, and RNase E may function in the maturation of sRNAs. Most sRNAs locally distribute across the 15 reference genomes of Alcanivorax, and only 7.5% of sRNAs are broadly conserved in this genus. Expression responses to the alkane of several core conserved sRNAs, including 6S RNA, M1 RNA and tmRNA, indicate that they may participate in alkane metabolisms and result in more actively global transcription, RNA processing and stresses mitigation. Two novel CsrA-related sRNAs are identified, which may be involved in the translational activation of alkane metabolism-related genes by sequestering the global repressor CsrA. The relationships of sRNAs with the characterized genes of alkane sensing (ompS), chemotaxis (mcp, cheR, cheW2), transporting (ompT1, ompT2, ompT3) and hydroxylation (alkB1, alkB2, almA) were created based on the genome-wide predicted sRNA-mRNA interactions. Overall, the sRNA landscape lays the ground for uncovering cryptic regulations in critical marine bacterium, among which both the core and species-specific sRNAs are implicated in the alkane adaptive metabolisms.
Subject(s)
Alcanivoraceae , RNA, Small Untranslated , Alcanivoraceae/genetics , Alcanivoraceae/metabolism , Ecosystem , RNA, Bacterial/genetics , RNA, Bacterial/metabolism , Base Sequence , RNA, Small Untranslated/genetics , RNA, Small Untranslated/metabolism , Gene Expression Regulation, BacterialABSTRACT
White spot syndrome virus (WSSV) can cause a contagious, high virulent and pandemic disease for crustaceans, especially shrimps. However, the molecular mechanism of WSSV pathogenesis remains unclear. Flotillins are lipid raft-associated proteins, which mainly include flotillin-1 and flotillin-2. They are involved in the formation of large heteromeric protein complexes engaged in diverse signalling pathways at the membrane-cytosol interface. They defined a clathrin-independent endocytic pathway in mammalian cells. Our previous studies suggested that shrimp flotillin-2 might mediate endocytosis involved in WSSV infection. To further explore the function of shrimp flotillin, a flotillin-1 homologous, Lvflotillin-1A was identified and characterized in Litopenaeus vanamei. The transcription of Lvflotillin-1A showed a significant decline at 12h post-infection, followed by complete recovery and a slight up-regulation after the WSSV challenge. Gene silencing revealed that inhibition of Lvflotillin-1A raised the virus infection, suggesting Lvflotillin-1A might play an important role in shrimp immunity. Furthermore, co-immunoprecipitation and immunofluorescence illustrated that Lvflotillin-1A and Lvflotillin-2 could form hetero-oligomers, and co-expression promoted the accumulation of intracellular vesicles. The study revealed that WSSV might up-regulate Lvflotillin-2 expression and alter the subcellular location of Lvflotillin-1 protein to facilitate virus infection. These results will provide information for understanding the interaction between WSSV and shrimp.
Subject(s)
Penaeidae , White spot syndrome virus 1 , Animals , Arthropod Proteins , Clathrin , Mammals/metabolism , Membrane Microdomains/metabolism , White spot syndrome virus 1/physiologyABSTRACT
Nuclear DNA-binding TCF proteins, which act as the main downstream effectors of Wnt signaling, are essential for the regulation of cell fate and innate immunity. However, their role during viral infection in shrimp remains unknown. Herein, we demonstrated that Litopenaeus vannamei TCF (LvTcf) acts independently of Lvß-catenin to promote interferon-like protein LvVago1 production, thus mounting the response to WSSV infection. Further, we observed that WSV083, a WSSV serine/threonine protein kinase, bound to LvTcf and phosphorylated it. Phosphorylated LvTcf was then recognized and degraded via the ubiquitin-proteasome pathway. Moreover, mass spectrometry analyses indicated that the T39 and T104 residues of LvTcf were target sites phosphorylated by WSV083. Point mutation analyses suggested that additional sites of LvTcf may undergo phosphorylation via WSV083. Taken together, the current work provides valuable insights into host immunity and viral pathogenesis. LvTcf is not only a modulator of shrimp innate immunity but is also an important target for WSSV immune evasion. Thus, the current findings will help improve disease control in shrimps.
Subject(s)
DNA Virus Infections/virology , Penaeidae/immunology , Penaeidae/virology , TCF Transcription Factors/immunology , White spot syndrome virus 1/pathogenicity , Animals , Arthropod Proteins/immunology , Arthropod Proteins/metabolism , DNA Virus Infections/immunology , DNA Virus Infections/metabolism , Host-Pathogen Interactions/immunology , Immunity, Innate/immunology , Penaeidae/metabolism , Phosphorylation , TCF Transcription Factors/metabolism , Viral ProteinsABSTRACT
We present a general method for approximately contracting tensor networks with an arbitrary connectivity. This enables us to release the computational power of tensor networks to wide use in inference and learning problems defined on general graphs. We show applications of our algorithm in graphical models, specifically on estimating free energy of spin glasses defined on various of graphs, where our method largely outperforms existing algorithms, including the mean-field methods and the recently proposed neural-network-based methods. We further apply our method to the simulation of random quantum circuits and demonstrate that, with a trade-off of negligible truncation errors, our method is able to simulate large quantum circuits that are out of reach of the state-of-the-art simulation methods.
ABSTRACT
BACKGROUND: The false positive in conventional syphilis serological test was found in patients with multiple myeloma (MM). OBJECTIVE: To investigate the relationship between the M-protein of patients with MM and the false positive in conventional syphilis serologic test. METHODS: The M-protein of 68 MM cases was typed with immunofixation electrophoresis and 68 cases of MM were screened with non-specific and specific syphilis serologic tests, then the samples with syphilic serological positive were chosen and confirmed with immonobloting test, finally the relationship between M protein of MM and the false positive of syphilis serological test were analysed. RESULTS: Four out of 68 cases showed the positive in syphilis serological test and further were confimed to be false positive by immunoblotting test, the false positive rate was nearly 6%. The M-protein of MM patients in our hospital mostly possessed IgG, κ type, followed by IgA, κ type, light chain κ type. In general, κ : λ = 2.4 : 1. Among samples of 4 cases with syphilis serological positive 2 cases were of IgG and κ type, 1 case was of IgG, λ type, another 1 case was IgA, κ type. CONCLUSION: The M-protein of IgG and IgA types in MM patients results in syphilis serological false positive reaction. The clinicians and laboratorial technicians should pay a great attention to screen the MM patients for the false positive syphilis serological test so as to avoid the misdiagnosis and subsequent embarassment.
Subject(s)
Multiple Myeloma/diagnosis , Myeloma Proteins/metabolism , Syphilis Serodiagnosis , Syphilis/diagnosis , Diagnostic Errors , False Positive Reactions , Humans , Immunoglobulin A/classification , Immunoglobulin G/classificationABSTRACT
A series of novel IMB-070593 derivatives containing a substituted benzyloxime moiety and displaying a remarkable improvement in lipophilicity were synthesized and evaluated for their in vitro antimycobacterial and antibacterial activity. Our results reveal that the target compounds 19a-m have considerable Gram-positive activity (MIC: <0.008-32 µg/mL), although they are generally less active than the reference drugs against the Gram-negative strains. In particular, compounds 19h, 19j, 19k and 19m show good activity (MICs: <0.008-4 µg/mL) against all of the tested Gram-positive strains, including ciprofloxacin (CPFX)- and/or levofloxacin (LVFX)-resistant MSSA, MRSA and MSSE. Moreover, compound 19l (MIC: 0.125 µg/mL) is found to be 2-4 fold more active than the parent IMB070593, CPFX and LVFX against M. tuberculosis H37Rv ATCC 27294.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Oximes/pharmacology , Piperidines/pharmacology , Ciprofloxacin/pharmacology , Gram-Negative Bacteria/drug effects , Levofloxacin , Magnetic Resonance Spectroscopy , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Ofloxacin/pharmacology , Staphylococcus aureus/drug effectsABSTRACT
A series of novel gemifloxacin (GMFX) derivatives containing a substituted benzyloxime moiety with remarkable improvement in lipophilicity were synthesized. The target compounds evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that most of the target compounds have considerable potency against all of the tested gram-positive strains including MRSA and MRSE (MIC: <0.008-8 µg/mL), although they are generally less active than the references against the gram-negative strains. In particular, compound 11l (MIC: <0.008-4 µg/mL) was found to be 8-2048 and 2-128 times more potent than levofloxacin (LVFX) and GMFX against the gram-positive strains, respectively. Moreover, against MRSA clinical isolates, 11l (MIC(90): 1 µg/mL) is 8-fold more active than GMFX, and 2-fold more active than GMFX and moxifloxacin against MRSE clinical isolates (MIC(90): 4 µg/mL).
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Fluoroquinolones/chemical synthesis , Fluoroquinolones/pharmacology , Naphthyridines/chemical synthesis , Naphthyridines/pharmacology , Oximes/chemistry , Anti-Bacterial Agents/chemistry , Chemistry Techniques, Synthetic , Fluoroquinolones/chemistry , Gemifloxacin , Hydrophobic and Hydrophilic Interactions , Microbial Sensitivity Tests , Naphthyridines/chemistryABSTRACT
A series of novel gatifloxacin (GTFX) derivatives were designed, synthesized and characterized by (1)H NMR, (13)C NMR, MS and HRMS. These derivatives were evaluated for in vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Our results reveal that most of the target compounds show good potency in inhibiting the growth of Staphylococcus aureus including MRSA and Staphylococcus epidermidis including MRSE. Compounds 8, 14 and 20 have useful activity against all of the tested Gram-positive and Gram-negative strains (MICs: 0.06-4 µg/mL). In particular, 20 possessing a broad antimicrobial spectrum (MICs: 0.06-1 µg/mL) was found to be 2-32-folds more potent than the reference drug levofloxacin and parent GTFX against Pseudomonas aeruginosa.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Fluoroquinolones/chemical synthesis , Fluoroquinolones/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Cell Survival/drug effects , Chlorocebus aethiops , Fluoroquinolones/chemistry , Gatifloxacin , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , In Vitro Techniques , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Spectrometry, Mass, Fast Atom Bombardment , Vero CellsABSTRACT
A series of novel 7-(3-alkoxyimino-4-amino-4-methylpiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized and evaluated for their in vitro antibacterial activity and cytotoxicity. All of the target compounds have potent antibacterial activity against the tested Gram-positive and Gram-negative strains, and exhibit good potency in inhibiting the growth of Staphylococcus aureus including MRSA, Staphylococcus epidermidis including MRSE and Streptococcus pneumoniae (MICs: 0.125-4 µg/mL). Compound 22, with the best activity against Gram-positive strains, is 4-16 fold more potent than gemifloxacin, gatifloxacin and levofloxacin against Enterococcus faecalis, and 16- and 4-fold more potent than levofloxacin against S. epidermidis 09-6 and S. pneumoniae 08-4, respectively.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Fluoroquinolones/pharmacology , Staphylococcus/drug effects , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Cell Line , Cell Survival/drug effects , Crystallography, X-Ray , Dogs , Dose-Response Relationship, Drug , Drug Design , Drug Evaluation, Preclinical , Fluoroquinolones/chemical synthesis , Fluoroquinolones/chemistry , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Staphylococcus/growth & development , Stereoisomerism , Structure-Activity RelationshipABSTRACT
OBJECTIVE: To investigate whether down-regulation of Twist1 could change sensitivity of nasopharyngeal carcinoma cell line HNE1 to taxol. METHODS: HNE1 cells were transfected with the small interfering RNA (siRNA) expression vector pSuppressor-Retro-Si-Twist, containing the short hairpin RNA (shRNA) sequence targeting the Twist gene-coding region by Fugene 6. Positive clones were then selected in Neomycin (400 microg/ml) for 21 days. The low expressions of Twist1 were examined by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blot. Drug sensitivity of si-Twist1 HNE1 to taxol was determined by Annexin V-fluorescein isothiocyanate( FITC)/propidium lodide (PI) double-labeled flow cytometry and detection of DNA ladder. The Effect of Twist1 inactivation on HNE1 cell proliferation was observed by MTT assay and flow cytometry. RESULTS: Annexin V- FITC-PI assay showed that apoptosis ratio was 40.2% in si-Twist HNE1 after treated with 10 ng/ml taxol, significantly higher than that in the control siRNA group 24.3%. The deference had statistic meaning. After the re-expression of HNE1, apoptosis ratio was 44.80% +/- 4.80% (x +/- s) in low Twist1 protein expression group and that was 27.00% +/- 2.91% in high expression group. The deference had statistic meaning (t = 4.374, P = 0.049). Real time PCR test revealed apoptosis protein bcl-2 expression in si-Twist HNE1 was 0.28 +/- 0.05, significantly lower than that in the control siRNA HNE1 (0.57 +/- 0.08, t = 6.710, P = 0.021), nevertheless, significant bax and bcl-XL changes were not observed (t = 2.000, P = 0.184 and t = 1.502, P = 0.272). MTT and FCM showed that down-regulation of Twist1 did not alter cell proliferation rate (P>0.05). CONCLUSIONS: Down-regulation of Twist1 could increase drug sensitivity of nasopharyngeal carcinoma cell line HNE1 to taxol by inducing apoptosis. These results suggested that Twist1 may be a promising treatment target for nasopharyngeal carcinoma therapy.
Subject(s)
Apoptosis/drug effects , Nasopharyngeal Neoplasms/drug therapy , Nuclear Proteins/genetics , Paclitaxel/pharmacology , Twist-Related Protein 1/genetics , Cell Line, Tumor , Down-Regulation , Gene Expression Regulation, Neoplastic , Humans , RNA Interference , RNA, Small InterferingABSTRACT
OBJECTIVE: To explore the relationship between genetic polymorphisms of C-344T in the promoter region and K173R in the exon 3 of aldosterone synthase gene (CYP11B2) and the incidence of essential hypertension in a northern Chinese Han population. METHODS: We conducted a case-control study including 182 hypertensive patients and 189 healthy controls in Harbin newspaper office and assayed the genotypes of C-344T and K173R using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technology. RESULTS: The distributions of C-344T and K173R genotype frequencies in men and women were in accordance with the Hardy-Weinberg equilibrium. The differences of C-344T allele and genotype as well as K173R allele frequency distributions between hypertensive patients and healthy controls were not statistically significant in men and women and pooled population (P > or = 0.05). The difference of K173R genotype frequency distribution reached borderline significance (P = 0.0500) and was more pronounced in women (P = 0.0038) according to the dominant mode of inheritance. Moreover, the magnitude of this mode of inheritance was more remarkable after the confounding factors were adjusted. K173R statistically correlated with the systolic hypertension in women. CONCLUSION: The CYP11B2 K173R polymorphism correlates with the susceptibility of essential hypertension in the northern Chinese Han population.