The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment.

Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment.

Comprehensive pan-cancer analysis of inflammatory age-clock-related genes as prognostic and immunity markers based on multi-omics data.

Inflammatory age (iAge) is a vital concept for understanding the intricate interplay between chronic inflammation and aging in the context of cancer. However, the importance of iAge-clock-related genes (iAge-CRGs) across cancers remains unexplored. This study aimed to explore the mechanisms and applications of these genes across diverse cancer types. We analyzed profiling data from over 10,000 individuals, covering 33 cancer types, 750 small molecule drugs, and 24 immune cell types. We focused on DCBLD2's function at the single-cell level and computed an iAge-CRG score using GSVA. This score was correlated with cancer pathways, immune infiltration, and survival. A signature was then derived using univariate Cox and LASSO regression, followed by ROC curve analysis, nomogram construction, decision curve analysis, and immunocytochemistry. Our comprehensive analysis revealed epigenetic, genomic, and immunogenomic alterations in iAge-CRGs, especially DCBLD2, leading to abnormal expression. Aberrant DCBLD2 expression strongly correlated with cancer-associated fibroblast infiltration and prognosis in multiple cancers. Based on GSVA results, we developed a risk model using five iAge-CRGs, which proved to be an independent prognostic index for uveal melanoma (UVM) patients. We also systematically evaluated the correlation between the iAge-related signature risk score and immune cell infiltration. iAge-CRGs, particularly DCBLD2, emerge as potential targets for enhancing immunotherapy outcomes. The strong correlation between abnormal DCBLD2 expression, cancer-associated fibroblast infiltration, and patient survival across various cancers underscores their significance. Our five-gene risk signature offers an independent prognostic tool for UVM patients, highlighting the crucial role of these genes in suppressing the immune response in UVM.Kindly check and confirm whether the corresponding affiliation is correctly identified.I identified the affiliation is correctly.thank you.Per style, a structured abstract is not allowed so we have changed the structured abstract to an unstructured abstract. Please check and confirm.I confirm the abstract is correctly ,thank you.

Circulating metabolic biomarkers and risk of new-onset hypertension: findings from the UK Biobank.

OBJECTIVE: The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension. METHODS: We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). RESULTS: During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24-1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66-0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence. CONCLUSION: Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.

Cross-domain heterogeneous metasurface inverse design based on a transfer learning method.

In this Letter, a transfer learning method is proposed to complete design tasks on heterogeneous metasurface datasets with distinct functionalities. Through fine-tuning the inverse design network and freezing the parameters of hidden layers, we successfully transfer the metasurface inverse design knowledge from the electromagnetic-induced transparency (EIT) domain to the three target domains of EIT (different design), absorption, and phase-controlled metasurface. Remarkably, in comparison to the source domain dataset, a minimum of only 700 target domain samples is required to complete the training process. This work presents a significant solution to lower the data threshold for the inverse design process and provides the possibility of knowledge transfer between different domain metasurface datasets.

[In vitro and in vivo validation of cytotoxicity of targeting human epidermal growth factor receptor-2 chimeric antigen receptor T (HER2-CAR-T) cells].

Objective To evaluate the toxicology of targeting human epidermal growth factor receptor-2 chimeric antigen receptor T (HER2-CAR-T) cells and to provide a safety basis for the clinical evaluation of HER2-CAR-T cell therapy. Methods The recombinant lentiviral vector was used to generate HER2-CAR-T cells. Soft agar colony formation assay was used to observe the colony formation of HER2-CAR-T cells, and the colony formation rate was statistically analyzed. The HER2-CAR-T cell suspension was co-incubated with rabbit red blood cell suspension, and the hemolysis of red blood cells was evaluated by direct observation and microplate reader detection. The HER2-CAR-T cell preparation was injected into the ear vein of male New Zealand rabbits, and the stimulating effect of HER2-CAR-T cells on the blood vessels of the animals was observed by staining of tissue sections. The vesicular stomatitis virus envelope glycoprotein (VSV-G) gene of pMD 2.G vector was used as the target sequence, and the safety of the lentiviral vector was verified by real-time fluorescence quantitative PCR. The heart, liver, lung, and kidney of mice receiving HER2-CAR-T cell infusion were collected, and the lesions were observed by HE staining. Results The HER2-CAR-T cells were successfully prepared. These cells did not exhibit soft agar colony formation ability in vitro, and the HER2-CAR-T cell preparation did not cause hemolysis in New Zealand rabbit red blood cells. After the infusion of HER2-CAR-T cells into the ear vein of New Zealand rabbits, no obvious vascular stimulation response was found, and no specific amplification of VSV-G was detected. No obvious lesions were found in the heart, liver, lung and kidney tissues of the treatment group. Conclusion The prepared HER2-CAR-T cells have reliable safety.

Unilateral biportal endoscopy vs. open decompression for lumbar epidural lipomatosis-cohort study using a prospective registry.

Objective: This study aimed to compare the outcomes of unilateral biportal endoscopy, unilateral laminectomy bilateral decompression (UBE-ULBD), and open lumbar decompression (OLD) in patients with lumbar epidural lipomatosis (LEL). Methods: This prospective observational study was conducted from March 2019 to May 2022 and encompassed 33 patients with LEL who underwent lumbar decompression. The study included 15 cases of UBE-ULBD decompression and 18 cases of open decompression, which were followed up for 1 year. The baseline characteristics, initial clinical manifestations, and surgical details [including estimated blood loss (EBL) and preoperative complications] of all patients were recorded. Radiographic evaluation included the cross-sectional area (CSA) of the thecal sac and paraspinal muscles on MRI. Clinical results were analyzed using the Short Form-36 Score (SF-36), the Numeric Pain Rating Scale (NRS) for lumbar and leg pain, creatine kinase, the Roland and Morris Disability Questionnaire (RMDQ), and the Oswestry Disability Index (ODI). Results: The dural sac CSA increased considerably at the 1-year postoperative follow-up in both groups (p < 0.001). The operative duration in the OLD group (48.2 ± 7.2 min) was shorter than that in the UBE-ULBD group (67.7 ± 6.3 min, p < 0.001). The OLD group (97.2 ± 19.8 mL) was associated with more EBL than the UBE-ULBD group (40.6 ± 13.6 mL, p < 0.001). The duration of hospitalization in the OLD group (5.4 ± 1.3 days) was significantly longer compared with the UBE-ULBD group (3.5 ± 1.2 days, p < 0.01). The SF-36, NRS, RMDQ, and ODI scores improved in both groups postoperatively (p < 0.001). Serum creatine kinase values in the UBE-ULBD group (101.7 ± 15.5) were significantly lower than those in the OLD group (330.8 ± 28.1 U/L) 1 day after surgery (p < 0.001). The degree of paraspinal muscle atrophy in the UBE-ULBD group (4.81 ± 1.94) was significantly lower than that in the OLD group (12.15 ± 6.99) at 1 year (p < 0.001). Conclusion: UBE-ULBD and OLD demonstrated comparable clinical outcomes in treating LEL. However, UBE-ULBD surgery was associated with shorter hospital stays, lower rates of incision infection, lighter paravertebral muscle injury, and lower EBL than OLD surgery. Consequently, UBE-ULBD can be recommended in patients with LEL if conservative treatment fails.

Augmented antitumor immune responses of HER2-targeted pyroptotic induction by long-lasting recombinant immunopyroptotins.

Pyroptosis is a well-documented form of programmed cell death caused by the gasdermin-driven perforation of cell membranes. Selective induction of pyroptosis in tumor cells represents a promising antitumor strategy to enhance the efficacy of immunotherapy. In this study, we established a recombinant protein-based immunopyroptotin strategy that led to the intratumoral induction of pyroptosis for HER2-directed therapy. Long-lasting immunopyroptotins were constructed by sequentially fusing the humanized anti-HER2 single-chain antibody P1h3, albumin-binding peptide (ABD035 or dAb7h8), cathepsin B-cleavable peptide B2, endosome-disruptive peptide E5C3, and active pyroptotic effector gasdermin D-N fragment (GN). After purification, we evaluated the cytotoxicity and antitumor immune responses primarily induced by the immunopyroptotins in HER2-overexpressing breast cancer cells. The resulting ABD035-immunoGN and dAb7h8-immunoGN showed improved in vitro cytotoxicity in HER2-overexpressing cancer cells compared with that in the immunotBid that we previously generated to induce tumor cell apoptosis. The binding of long-lasting immunopyroptotins to albumin increased the half-life by approximately 7-fold in nude mice. The enhanced antitumor efficacy of long-lasting immunopyroptotins was confirmed in both N87 tumor-bearing T cell-deficient mice and 4T1-hHER2 bilateral tumor-bearing immunocompetent mice. Immunopyroptotin treatment elicited systemic antitumor immune responses involving CD8+ T cells and mature dendritic cells and upregulated the expression of proinflammatory cytokines, leading to sustained remission of non-injected distant tumors. This study extends the repertoire of antibody-based therapeutics through the tumor-targeted delivery of a constitutively active pore-forming gasdermin-N fragment, which shows great potential for pyroptosis-based antitumor therapy.

Effectiveness of Blended Versus Traditional Refresher Training for Cardiopulmonary Resuscitation: Prospective Observational Study.

BACKGROUND: Generally, cardiopulmonary resuscitation (CPR) skills decline substantially over time. By combining web-based self-regulated learning with hands-on practice, blended training can be a time- and resource-efficient approach enabling individuals to acquire or refresh CPR skills at their convenience. However, few studies have evaluated the effectiveness of blended CPR refresher training compared with that of the traditional method. OBJECTIVE: This study investigated and compared the effectiveness of traditional and blended CPR training through 6-month and 12-month refresher sessions with CPR ability indicators. METHODS: This study recruited participants aged ≥18 years from the Automated External Defibrillator Donation Project. The participants were divided into 4 groups based on the format of the CPR training and refresher training received: (1) initial traditional training (a 30-minute instructor-led, hands-on session) and 6-month traditional refresher training (Traditional6 group), (2) initial traditional training and 6-month blended refresher training (an 18-minute e-learning module; Mixed6 group), (3) initial traditional training and 12-month blended refresher training (Mixed12 group), and (4) initial blended training and 6-month blended refresher training (Blended6 group). CPR knowledge and performance were evaluated immediately after initial training. For each group, following initial training but before refresher training, a learning effectiveness assessment was conducted at 12 and 24 months. CPR knowledge was assessed using a written test with 15 multiple-choice questions, and CPR performance was assessed through an examiner-rated skill test and objectively through manikin feedback. A generalized estimating equation model was used to analyze changes in CPR ability indicators. RESULTS: This study recruited 1163 participants (mean age 41.82, SD 11.6 years; n=725, 62.3% female), with 332 (28.5%), 270 (23.2%), 258 (22.2%), and 303 (26.1%) participants in the Mixed6, Traditional6, Mixed12, and Blended6 groups, respectively. No significant between-group difference was observed in knowledge acquisition after initial training (P=.23). All groups met the criteria for high-quality CPR skills (ie, average compression depth: 5-6 cm; average compression rate: 100-120 beats/min; chest recoil rate: >80%); however, a higher proportion (98/303, 32.3%) of participants receiving blended training initially demonstrated high-quality CPR skills. At 12 and 24 months, CPR skills had declined in all the groups, but the decline was significantly higher in the Mixed12 group, whereas the differences were not significant between the other groups. This finding indicates that frequent retraining can maintain high-quality CPR skills and that blended refresher training is as effective as traditional refresher training. CONCLUSIONS: Our findings indicate that 6-month refresher training sessions for CPR are more effective for maintaining high-quality CPR skills, and that as refreshers, self-learning e-modules are as effective as instructor-led sessions. Although the blended learning approach is cost and resource effective, factors such as participant demographics, training environment, and level of engagement must be considered to maximize the potential of this approach. TRIAL REGISTRATION: IGOGO NCT05659108; https://www.cgmh-igogo.tw.

Composition, characteristics, and treatment technologies of condensable particulate matter present in flue gas emitted by coking plants in China.

To study the total particulate matter (TPM) in flue gas emitted by coking plants, a sampling system that could be used to collect filterable particulate matter (FPM) and condensable particulate matter (CPM) was designed and developed based on Method 202 recommended by the U.S. Environmental Protection Agency in 2017 and HJ 836-2017 issued by China. Using this system, FPM and CPM in flue gas emitted by four coking furnaces named A, B, C, and D were tested in China. Further, 9 water-soluble ions, 20 elements, and organic matter present in the CPM were simultaneously examined to determine their formation mechanisms. Statistical data suggested that the FPM emission level in the coking flue gas was low and the average mass concentration was less than 10 mg/m3. However, with high CPM and TPM emission levels, the TPM mass concentrations of A, B, C, and D were 130 ± 11.1, 84.4 ± 6.36, 35.1 ± 17.0, and 63.8 ± 13.0 mg/m3, respectively. The main component of TPM was CPM, and the average mass concentration of CPM accounted for 98%, 95%, 68%, and 95% of TPM in furnaces A, B, C, and D, respectively. Water-soluble ions were the important components of CPM, and the total concentration of water-soluble ions accounted for 70%, 87%, 42%, and 66% of CPM in furnaces A, B, C, and D, respectively. Toxic and harmful heavy metals, such as Mn, Cr, Ni, Cu, Zn, As, Cd, and Pb, were detected in CPM. The formation mechanism of CPM was analyzed in combination with flue-gas treatment. It was shown that the treatment process "activated carbon- flue-gas countercurrent-integrated purification technology + ammonia spraying" used in furnaces A and B was less effective in removing CPM, water-soluble ions, metals, and compounds than that of "selective catalytic reduction denitrification + limestone-gypsum wet desulfurization (spraying NaOH solution)" in furnaces C and D. Hence, different flue-gas treatment technologies and operation levels played vital roles in the formation, transformation, and removal of CPM from flue-gas. Organic components in CPM discharged from furnace A were determined via gas chromatography-mass spectrometry, and the top 15 organic components in CPM were obtained using the area normalization method. N-alkanes accounted for the highest proportion, followed by esters and phenols, and most of them were toxic and harmful to humans and ecosystems. Therefore, advanced CPM treatment technologies should be developed to reduce atmospheric PM2.5 and its precursors to improve ambient air quality in China.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma.

In this editorial, we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023. We focused on identifying risk factors for lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma (SESCC) patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients, thereby helping to guide the selection of an appropriate treatment plan. The current standard treatment for SESCC is radical esophagectomy with lymph node dissection. However, esophagectomy is associated with considerable morbidity and mortality. Endoscopic resection (ER) offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome. However, since ER is a localized treatment that does not allow for lymph node dissection, the risk of LNM in SESCC limits the effectiveness of ER. Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy. Previous studies have shown that tumor size, macroscopic type of tumor, degree of differentiation, depth of tumor invasion, and lymphovascular invasion are factors associated with LNM in patients with SESCC. In addition, tumor budding is commonly associated with LNM, recurrence, and distant metastasis, but this topic has been less covered in previous studies. By comprehensively evaluating the above risk factors for LNM, useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Constructing Highly Stable Zinc Metal Anodes via Induced Zn(002) Growth.

The nonuniform electric field at the surface of a zinc (Zn) anode, coupled with water-induced parasitic reactions, exacerbates the growth of Zn dendrites, presenting a significant impediment to large-scale energy storage in aqueous Zn-ion batteries. One of the most convenient strategies for mitigating dendrite-related issues involves controlling crystal growth through electrolyte additives. Herein, we present thiamine hydrochloride (THC) as an electrolyte additive capable of effectively stabilizing the preferential deposition of the Zn(002) plane. First-principles calculations reveal that THC tends to adsorb on Zn(100) and Zn(101) planes and is capable of inducing the deposition of Zn ion onto the (002) plane and the preferential growth of the (002) plane, resulting in a flat and compact deposition layer. A THC additive not only effectively suppresses dendrite growth but also prevents the generation of side reactions and hydrogen evolution reaction. Consequently, the Zn||Zn symmetric battery exhibits long-term cycling stability of over 3000 h at 1 mA cm-2/1 mAh cm-2 and 1000 h at 10 mA cm-2/10 mAh cm-2. Furthermore, the NH4V4O10||Zn full battery also displays excellent cycling stability and a high reversible capacity of 210 mAh g-1 after 1000 cycles at 1 A g-1, highlighting a significant potential for practical applications.

Covalently Bonded Heterostructures with Mixed-Dimensional Carbons for Suppressing Mechanochemical Wear of Diamond under Heavy Loads.

Diamond is widely acknowledged as the hardest naturally occurring material. Nevertheless, when exposed to friction against ferrous metals, it is prone to graphitization or amorphization, which limits the utilization of its extremely high hardness and wear resistance. These issues have persisted for decades without an effective solution. Here, we report that a covalently bonded heterostructure with mixed-dimensional carbons as a high-performance solid lubricant could effectively reduce diamond surface friction and mechanochemical wear with excellent load capacity and durability. When subjected to dry friction and heavy loads (20-150 N), the heterostructure exhibited a notable improvement over pristine diamond with reduced friction coefficients and relative wear rates by 22-45 and 67-91%, respectively. Especially under a 20 N load, the relative wear rate was an order of magnitude lower than that of pristine diamond. Additionally, experiments and molecular dynamics simulations revealed that the heterostructure integrated the outstanding properties of diamond (three-dimensional (3D)), nanographite (3D), and graphene (two-dimensional (2D)), resulting in improved lubrication and antiwear performance that could not be achieved by the individual carbon materials. The findings in this work will be beneficial to overcome the ferrous metal forbidden zone of diamond and are expected to expand the applications of engineered diamond surfaces and graphite/graphene in tribology, mechanics, and electronic fields.

Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

Comments on "Planar Tetracoordinate Hydrogen: Pushing the Limit of Multicentre Bonding".

In a recent communication (Angew. Chem. Int. Ed. 2024, 63, e202317312), Kalita et al. studied In4H+ system within the frame of single-reference approximation (SRA) and found that the global energy minimum (1 a) adopted the singlet state and a planar tetracoordinate hydrogen (ptH), while the second lowest isomer (1 b) located 3.0 kcal/mol above 1 a and adopted the triplet state as well as non-planar structure with a quasi-ptH. They assessed the reliability of SRA by checking the T1-diagnostic values of coupled cluster calculations. However, according to our multi-configurational second-order perturbation theory calculations at the CASPT2(12,13)/aug-cc-pVQZ (aug-cc-pVQZ-PP for In) level, both 1 a and 1 b exhibit obvious multi-referential characters, as reflected by their largest reference coefficients of 0.928 (86.1 %) and 0.938 (88.0 %), respectively. Moreover, 1 b is 5.05 kcal/mol lower than 1 a at this level, that is, what can be observed in In4H+ system is the quasi-ptH.

Triterpenoid saponins from Bupleurum marginatum and their anti-liver fibrotic activities.

A new triterpenoid saponin (1), along with five known compounds (2-6), was isolated from Bupleurum marginatum Wall. ex DC, of which compounds 2-4 were obtained for the first time from this plant. The structures were confirmed by the analysis of 1D, 2D NMR, and HR-ESIMS data, and comparison with previous spectral data. Anti-liver fibrotic activities of the isolates were determined as proliferation inhibition of LPS-induced activation of HSC-T6 in vitro.

Altered mucosal bacteria and metabolomics in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. AIM: This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. METHODS: The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. RESULTS: High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. CONCLUSION: This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Investigation of bioactive compounds and their correlation with the antioxidant capacity in different functional vinegars.

There are complex and diverse substances in traditional vinegars, some of which have been identified as biologically active factors, but the variety of functional compounds is currently restricted. In this study, it was aimed to determine the bioactive compounds in 10 typical functional vinegars. The findings shown that total flavonoids (0.21-7.19 mg rutin equivalent/mL), total phenolics (0.36-3.20 mg gallic acid equivalent/mL), and antioxidant activities (DPPH: 3.17-47.63 mmol trolox equivalent/L, ABTS: 6.85-178.29 mmol trolox equivalent/L) varied among different functional vinegars. In addition, the concentrations of the polysaccharides (1.17-44.87 mg glucose equivalent/mL) and total saponins (0.67-12.46 mg oleanic acid equivalent/mL) were determined, which might play key role for the function of tested vinegars. A total of 8 organic acids, 7 polyphenol compounds and 124 volatile compounds were measured and tentatively identified. The protocatechuic acid (4.81-485.72 mg/L), chlorogenic acid (2.69-7.52 mg/L), and epicatechin (1.18-97.42 mg/L) were important polyphenol compounds in the functional vinegars. Redundancy analysis indicated that tartaric acid, oxalic acid and chlorogenic acid were significantly positively correlated with antioxidant capacity. Various physiologically active ingredients including cyclo (Pro-Leu), cyclo (Phe-Pro), cyclo (Phe-Val), cyclo (Pro-Val), 1-monopalmitin and 1-eicosanol were firstly detected in functional vinegars. Principle component analysis revealed that volatiles profile of bergamot Monascus aromatic vinegar and Hengshun honey vinegar exhibited distinctive differences from other eight vinegar samples. Moreover, the partial least squares regression analysis demonstrated that 11 volatile compounds were positively correlated with the antioxidant activity of vinegars, which suggested these compounds might be important functional substances in tested vinegars. This study explored several new functionally active compounds in different functional vinegars, which could widen the knowledge of bioactive factor in vinegars and provide new ideas for further development of functional vinegar beverages.

Pretraining a foundation model for generalizable fluorescence microscopy-based image restoration.

Fluorescence microscopy-based image restoration has received widespread attention in the life sciences and has led to significant progress, benefiting from deep learning technology. However, most current task-specific methods have limited generalizability to different fluorescence microscopy-based image restoration problems. Here, we seek to improve generalizability and explore the potential of applying a pretrained foundation model to fluorescence microscopy-based image restoration. We provide a universal fluorescence microscopy-based image restoration (UniFMIR) model to address different restoration problems, and show that UniFMIR offers higher image restoration precision, better generalization and increased versatility. Demonstrations on five tasks and 14 datasets covering a wide range of microscopy imaging modalities and biological samples demonstrate that the pretrained UniFMIR can effectively transfer knowledge to a specific situation via fine-tuning, uncover clear nanoscale biomolecular structures and facilitate high-quality imaging. This work has the potential to inspire and trigger new research highlights for fluorescence microscopy-based image restoration.

Cognitive-behavioral therapy for patients with somatoform disorders: A pilot preliminary randomized controlled trial.

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.