Acute toxicity effects of pesticides on predatory snout mites (Trombidiformes: Bdellidae).

Predatory mites biologically control a range of arthropod crop pests and are often central to agricultural IPM strategies globally. Conflict between chemical and biological pest control has prompted increasing interest in selective pesticides with fewer off-target impacts on beneficial invertebrates, including predatory mites. However, the range of predatory mite species included in standardized pesticide toxicity assessments does not match the diversity of naturally occurring species contributing to biocontrol, with most testing carried out on species from the family Phytoseiidae (Mesostigmata). Here, we aim to bridge this knowledge gap by investigating the impacts of 22 agricultural pesticides on the predatory snout mite, Odontoscirus lapidaria (Kramer) (Trombidiformes: Bdellidae). Using internationally standardized testing methodologies, we identified several active ingredients with minimal impact on O. lapidaria mortality, including Bacillus thuringiensis, nuclear polyhedrosis virus, flonicamid, afidopyropen, chlorantraniliprole, and cyantraniliprole, which may therefore be good candidates for IPM strategies utilizing both chemical and biological control. Comparison of our findings with previous studies on Phytoseiid mites reveals important differences in responses to a number of chemicals between predatory mite families, including the miticides diafenthiuron and abamectin, highlighting the risk of making family-level generalizations from acute toxicity assessments. We also tested the impacts of several pesticides on a second Bdellidae species (Trombidiformes: Bdellidae) and found differences in the response to chlorpyrifos compared with O. lapidaria, further highlighting the taxon-specific nature of nontarget toxicity effects.

Vesicle-associated membrane protein 8 knockdown exerts anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on colorectal cancer cells by inhibition of the JAK/STAT3 pathway.

Vesicle-associated membrane protein 8 (VAMP8), a soluble n-ethylmaleimide-sensitive factor receptor protein, acts as an oncogenic gene in the progression of several malignancies. Nevertheless, the roles and mechanisms of VAMP8 in colorectal cancer (CRC) progression remain unknown. The expression and prognostic significance of VAMP8 in CRC samples were analyzed through bioinformatics analyses. Cell proliferation was detected using CCK-8 and EdU incorporation assays and apoptosis was evaluated via flow cytometry. Western blot analysis was conducted to examine the protein expression. Ferroptosis was evaluated by measurement of iron metabolism, lipid peroxidation, and glutathione (GSH) content. VAMP8 was increased in CRC samples relative to normal samples on the basis of GEPIA and HPA databases. CRC patients with high level of VAMP8 had a worse overall survival. VAMP8 depletion led to a suppression of proliferation and promotion of apoptosis in CRC cells. Additionally, VAMP8 knockdown suppressed beclin1 expression and LC3-II/LC3-I ratio, elevated p62 expression, increased Fe2+, labile iron pool, lipid reactive oxygen species, and malondialdehyde levels, and repressed GSH content and glutathione peroxidase activity. Moreover, VAMP8 knockdown inhibited the activation of janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway in CRC cells. Mechanistically, activation of the JAK/STAT3 pathway by JAK1 or JAK2 overexpression attenuated VAMP8 silencing-mediated anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on CRC cells. In conclusion, VAMP8 knockdown affects the proliferation, apoptosis, autophagy, and ferroptosis by the JAK/STAT3 pathway in CRC cells.

Whole-genome resequencing reveals diversity and selective signals in the Wuxue goat.

Animal genetic resources are crucial for ensuring global food security. However, in recent years, a noticeable decline in the genetic diversity of livestock has occurred worldwide. This decline is pronounced in developing countries, where the management of these resources is insufficient. In the current study, we performed whole genome sequencing for 20 Wuxue (WX) and five Guizhou White (GW) goats. Additionally, we utilized the published genomes of 131 samples representing five different goat breeds from various regions in China. We investigated and compared the genetic diversity and selection signatures of WX goats. Whole genome sequencing analysis of the WX and GW populations yielded 120 425 063 SNPs, which resided primarily in intergenic and intron regions. Population genetic structure revealed that WX exhibited genetic resemblance to GW, Chengdu Brown, and Jintang Black and significant differentiation from the other goat breeds. In addition, three methods (nucleotide diversity, linkage disequilibrium decay, and runs of homozygosity) showed moderate genetic diversity in WX goats. We used nucleotide diversity and composite likelihood ratio methods to identify within-breed signatures of positive selection in WX goats. A total of 369 genes were identified using both detection methods, including genes related to reproduction (GRID2, ZNF276, TCF25, and SPIRE2), growth (HMGA2 and GJA3), and immunity (IRF3 and SRSF3). Overall, this study explored the adaptability of WX goats, shedding light on their genetic richness and potential to thrive in challenges posed by climatic changes and diseases. Further investigations are warranted to harness these insights to enhance more efficient and sustainable goat breeding initiatives.

Genetic Complexities of Cerebral Small Vessel Disease, Blood Pressure, and Dementia.

Importance: Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain. Objective: To investigate the causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and dementia risk, while accounting for potential epidemiologic biases. Design, Setting, and Participants: This study first examined the association of genetically determined WMH burden, stroke, and BP levels with Alzheimer disease (AD) in a 2-sample mendelian randomization (2SMR) framework. Second, using population-based studies (1979-2018) with prospective dementia surveillance, the genetic association of WMH, stroke, and BP with incident all-cause dementia was examined. Data analysis was performed from July 26, 2020, through July 24, 2022. Exposures: Genetically determined WMH burden and BP levels, as well as genetic liability to stroke derived from genome-wide association studies (GWASs) in European ancestry populations. Main Outcomes and Measures: The association of genetic instruments for WMH, stroke, and BP with dementia was studied using GWASs of AD (defined clinically and additionally meta-analyzed including both clinically diagnosed AD and AD defined based on parental history [AD-meta]) for 2SMR and incident all-cause dementia for longitudinal analyses. Results: In 2SMR (summary statistics-based) analyses using AD GWASs with up to 75 024 AD cases (mean [SD] age at AD onset, 75.5 [4.4] years; 56.9% women), larger WMH burden showed evidence for a causal association with increased risk of AD (odds ratio [OR], 1.43; 95% CI, 1.10-1.86; P = .007, per unit increase in WMH risk alleles) and AD-meta (OR, 1.19; 95% CI, 1.06-1.34; P = .008), after accounting for pulse pressure for the former. Blood pressure traits showed evidence for a protective association with AD, with evidence for confounding by shared genetic instruments. In the longitudinal (individual-level data) analyses involving 10 699 incident all-cause dementia cases (mean [SD] age at dementia diagnosis, 74.4 [9.1] years; 55.4% women), no significant association was observed between larger WMH burden and incident all-cause dementia (hazard ratio [HR], 1.02; 95% CI, 1.00-1.04; P = .07). Although all exposures were associated with mortality, with the strongest association observed for systolic BP (HR, 1.04; 95% CI, 1.03-1.06; P = 1.9 × 10-14), there was no evidence for selective survival bias during follow-up using illness-death models. In secondary analyses using polygenic scores, the association of genetic liability to stroke, but not genetically determined WMH, with dementia outcomes was attenuated after adjusting for interim stroke. Conclusions: These findings suggest that WMH is a primary vascular factor associated with dementia risk, emphasizing its significance in preventive strategies for dementia. Future studies are warranted to examine whether this finding can be generalized to non-European populations.

Cardiac Extracorporeal Membrane Oxygenation in Community Cardiac Surgery Program: Are the Results Comparable?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) outcomes in small centers are commonly considered less favorable than in large-volume centers. New ECMO protocols and procedures were established in our regional community hospital system as part of a cardiogenic shock initiative. This retrospective study aims to evaluate the outcomes of veno-arterial extracorporeal membrane oxygenation (VA ECMO) and extracorporeal cardiopulmonary resuscitation (ECPR) in a community hospital system with cardiac surgery capability and assess whether protocol optimization and cannulation standards result in comparable outcomes to larger centers whether the outcomes of this new ECMO program at the community hospital setting were comparable to the United States averages. METHODS: Our regional system comprises five hospitals with 1500 beds covering southwestern New Jersey, with only one of these hospitals having cardiac surgery and ECMO capability. In May 2021, the new ECMO program was initiated. Patients were screened by a multidisciplinary call, cannulated by our ECMO team, and subsequently treated by the designated team. We reviewed our cardiac ECMO outcomes over two years, from May 2021 to April 2023, in patients who required ECMO due to cardiogenic shock or as a part of extracorporeal cardiopulmonary resuscitation (ECPR). RESULTS: A total of 60 patients underwent cardiac ECMO, and all were VA ECMO, including 18 (30%) patients who required ECPR for cardiac arrest. The overall survival rate for our cardiac ECMO program turned out to be 48% (29/60), with 50% (22/42) in VA ECMO excluding ECPR and 39% (7/18) in the ECPR group. The hospital survival rate for the VA ECMO and ECPR groups was 36% (15/42) and 28% (5/18), respectively. The ELSO-reported national average for hospital survival is 48% for VA ECMO and 30% for ECPR. Considering these benchmarks, the hospital survival rate of our program did not significantly lag behind the national average. CONCLUSIONS: With protocol, cannulation standards, and ECMO management optimized, the VA ECMO results of a community hospital system with cardiac surgery capability were not inferior to those of larger centers.

How do probiotics alleviate constipation? A narrative review of mechanisms.

Constipation is a common gastrointestinal condition, which may occur at any age and affects countless people. The search for new treatments for constipation is ongoing as current drug treatments fail to provide fully satisfactory results. In recent years, probiotics have attracted much attention because of their demonstrated therapeutic efficacy and fewer side effects than pharmaceutical products. Many studies attempted to answer the question of how probiotics can alleviate constipation. It has been shown that different probiotic strains can alleviate constipation by different mechanisms. The mechanisms on probiotics in relieving constipation were associated with various aspects, including regulation of the gut microbiota composition, the level of short-chain fatty acids, aquaporin expression levels, neurotransmitters and hormone levels, inflammation, the intestinal environmental metabolic status, neurotrophic factor levels and the body's antioxidant levels. This paper summarizes the perception of the mechanisms on probiotics in relieving constipation and provides some suggestions on new research directions.

Transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae.

Congenital infection caused by vertical transmission of microsporidia N. bombycis can result in severe economic losses in the silkworm-rearing industry. Whole-transcriptome analyses have revealed non-coding RNAs and their regulatory networks in N. bombycis infected embryos and larvae. However, transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae remains unclear. Here, we simultaneously compared the transcriptomes of N. bombycis and its host B. mori embryos of 5-day and larvae of 1-, 5- and 10-day during congenital infection. For the transcriptome of N. bombycis, a comparison of parasite expression patterns between congenital-infected embryos and larva showed most genes related to parasite central carbon metabolism were down-regulated in larvae during infection, whereas the majority of genes involved in parasite proliferation and growth were up-regulated. Interestingly, a large number of distinct or shared differentially expressed genes (DEGs) were revealed by the Venn diagram and heat map, many of them were connected to infection related factors such as Ricin B lectin, spore wall protein, polar tube protein, and polysaccharide deacetylase. For the transcriptome of B. mori infected with N. bombycis, beyond numerous DEGs related to DNA replication and repair, mRNA surveillance pathway, RNA transport, protein biosynthesis, and proteolysis, with the progression of infection, a large number of DEGs related to immune and infection pathways, including phagocytosis, apoptosis, TNF, Toll-like receptor, NF-kappa B, Fc epsilon RI, and some diseases, were successively identified. In contrast, most genes associated with the insulin signaling pathway, 2-oxacarboxylic acid metabolism, amino acid biosynthesis, and lipid metabolisms were up-regulated in larvae compared to those in embryos. Furthermore, dozens of distinct and three shared DEGs that were involved in the epigenetic regulations, such as polycomb, histone-lysine-specific demethylases, and histone-lysine-N-methyltransferases, were identified via the Venn diagram and heat maps. Notably, many DEGs of host and parasite associated with lipid-related metabolisms were verified by RT-qPCR. Taken together, simultaneous transcriptomic analyses of both host and parasite genes lead to a better understanding of changes in the microsporidia proliferation and host responses in embryos and larvae in N. bombycis congenital infection.

Does local soil factor drive functional leaf trait variation? A test on Neilingding Island, South China.

Leaf traits were affected by soil factors and displayed varietal differences in forest. However, few examples have been reported on the Island ecosystems. We comprehensively investigated 9 leaf traits (leaf length, leaf width, leaf area, SLA, leaf fresh weight, leaf C content, leaf N content, leaf K content, leaf C:N ratio) of 54 main subtropical woody species and soil parameters (soil pH, total C content, total N content, total K content, available N content, available P content, available K content and soil moisture) in Neilingding Island, Shenzhen, southern China. Intra-and interspecific variation of leaf traits were measured and their correlations with soil parameters were explored. The interspecific variations of leaf C:N ratio, leaf N content and leaf fresh weight were higher than their intraspecific variations. The intraspecific variation of leaf K content was larger than that of interspecific one, accounting for 80.69% of the total variance. Positive correlations were found among intraspecific coefficients of variations in leaf morphological traits. The correlation analysis between the variation of intraspecific traits and the variation of soil parameters showed that changes in soil factors affected leaf morphology and stoichiometry. The interaction between soil moisture and soil available P content was the key factor on intraspecific variations of leaf traits including leaf area, leaf fresh weight, leaf C and leaf K content. We concluded that leaf traits of plants in the island were tightly related to soil parameters. Soil parameters, especially soil moisture and available P content, affected plant leaf morphology and stoichiometry at the local scale.

Bufei Huoxue capsule attenuates COPD-related inflammation and regulates intestinal microflora, metabolites.

Background: Bufei Huoxue capsule (BFHX) is widely used for the clinical treatment of chronic obstructive pulmonary disease (COPD) in China. Objectives: The aim of this study is to explore the effects on COPD and the underlying mechanism of BFHX. The process and methods: In this study, we established a COPD mouse model through cigarette smoke (CS) exposure in combination with lipopolysaccharide (LPS) intratracheal instillation. Subsequently, BFHX was orally administrated to COPD mice, and their pulmonary function, lung pathology, and lung inflammation, including bronchoalveolar lavage fluid (BALF) cell count and classification and cytokines, were analyzed. In addition, the anti-oxidative stress ability of BFHX was detected by Western blotting, and the bacterial diversity, abundance, and fecal microbiome were examined using 16S rRNA sequencing technology. Outcome: BFHX was shown to improve pulmonary function, suppress lung inflammation, decrease emphysema, and increase anti-oxidative stress, whereas 16S rRNA sequencing indicated that BFHX can dynamically regulate the diversity, composition, and distribution of the intestinal flora microbiome and regulate the lysine degradation and phenylalanine metabolism of COPD mice. These results highlight another treatment option for COPD and provide insights into the mechanism of BFHX.

Continuous operation of nano-catalytic ozonation using membrane separation coupling system: influence factors and mechanism.

The application of nano-catalysts in improving the ozonation removal efficiency for refractory organic compounds has been extensively investigated. However, cost-effective nano-catalysts separation remains a challenge. In this study, membrane separation processes were employed to separate nano-MgO catalysts from an ozonation system. A continuous nano-catalytic ozonation membrane separation (nCOMS) coupling system was successfully constructed for treating quinoline. The results showed that long hydraulic retention time (HRT) and high nano-MgO dosage could improve the quinolone removal efficiency but shorten operation cycles. At the optimal operation conditions of HRT=4 h and nano-MgO dosage=0.2 g/L, the nCOMS system achieved a stable quinoline removal efficiency of 85.2% for 240 min running with a transmembrane pressure lower than 10 kPa. The quinoline removal efficiency contribution for ozonation, catalysis and membrane separation was 57.1%, 24.9% and 18.0%, respectively. Compared to ozonation membrane separation system, the fouling rate index of the nCOMS system increased by 60% under optimal conditions, but the irreversible fouling was reduced to 28%. In addition, the nCOMS system exhibited reduced adverse effects of coexisting natural organic matter (NOM) on quinoline removal and membrane fouling. In conclusion, the nCOMS system demonstrated higher quinoline removal efficiency, lower irreversible fouling, and reduced adverse effect of coexisting NOM, thereby signifying its potential for practical applications in advanced treatment of industrial wastewater.

Essential Nutrients and White Matter Hyperintensities: A Two-Sample Mendelian Randomization Study.

Stroke and dementia have been linked to the appearance of white matter hyperintensities (WMHs). Meanwhile, diffusion tensor imaging (DTI) might capture the microstructural change in white matter early. Specific dietary interventions may help to reduce the risk of WMHs. However, research on the relationship between specific nutrients and white matter changes is still lacking. We aimed to investigate the causal effects of essential nutrients (amino acids, fatty acids, mineral elements, and vitamins) on WMHs and DTI measures, including fraction anisotropy (FA) and mean diffusivity (MD), by a Mendelian randomization analysis. We selected single nucleotide polymorphisms (SNPs) associated with each nutrient as instrumental variables to assess the causal effects of nutrient-related exposures on WMHs, FA, and MD. The outcome was from a recently published large-scale European Genome Wide Association Studies pooled dataset, including WMHs (N = 18,381), FA (N = 17,663), and MD (N = 17,467) data. We used the inverse variance weighting (IVW) method as the primary method, and sensitivity analyses were conducted using the simple median, weighted median, and MR-Egger methods. Genetically predicted serum calcium level was positively associated with WMHs risk, with an 8.1% increase in WMHs risk per standard deviation unit increase in calcium concentration (OR = 1.081, 95% CI = 1.006-1.161, p = 0.035). The plasma linoleic acid level was negatively associated with FA (OR = 0.776, 95% CI = 0.616-0.978, p = 0.032). Our study demonstrated that genetically predicted calcium was a potential risk factor for WMHs, and linoleic acid may be negatively associated with FA, providing evidence for interventions from the perspective of gene-environment interactions.

Long-term Intravital Investigation of an Orthotopic Glioma Mouse Model via Optical Coherence Tomography Angiography.

BACKGROUND/AIM: Probing brain tumor microvasculature holds significant importance in both basic cancer research and medical practice for tracking tumor development and assessing treatment outcomes. However, few imaging methods commonly used in clinics can noninvasively monitor the brain microvascular network at high precision and without exogenous contrast agents in vivo. The present study aimed to investigate the characteristics of microvasculature during brain tumor development in an orthotopic glioma mouse model. MATERIALS AND METHODS: An orthotopic glioma mouse model was established by surgical orthotopic implantation of U87-MG-luc cells into the mouse brain. Then, optical coherence tomography angiography (OCTA) was utilized to characterize the microvasculature progression within 14 days. RESULTS: The orthotopic glioma mouse model evaluated by bioluminescence imaging and MRI was successfully generated. As the tumor grew, the microvessels within the tumor area slowly decreased, progressing from the center to the periphery for 14 days. CONCLUSION: This study highlights the potential of OCTA as a useful tool to noninvasively visualize the brain microvascular network at high precision and without any exogenous contrast agents in vivo.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

A Fluorination Strategy and Low-Acidity Anchoring Group in Self-Assembled Molecules for Efficient and Stable Inverted Perovskite Solar Cells.

Herein, we synthesized two donor-acceptor (D-A) type small organic molecules with self-assembly properties, namely MPA-BT-BA and MPA-2FBT-BA, both containing a low acidity anchoring group, benzoic acid. After systematically investigation, it is found that, with the fluorination, the MPA-2FBT-BA demonstrates a lower highest occupied molecular orbital (HOMO) energy level, higher hole mobility, higher hydrophobicity and stronger interaction with the perovskite layer than that of MPA-BT-BA. As a result, the device based-on MPA-2FBT-BA displays a better crystallization and morphology of perovskite layer with larger grain size and less non-radiative recombination. Consequently, the device using MPA-2FBT-BA as hole transport material achieved the power conversion efficiency (PCE) of 20.32 % and remarkable stability. After being kept in an N2 glove box for 116 days, the unsealed PSCs' device retained 93 % of its initial PCE. Even exposed to air with a relative humidity range of 30±5 % for 43 days, its PCE remained above 91 % of its initial condition. This study highlights the vital importance of the fluorination strategy combined with a low acidity anchoring group in SAMs, offering a pathway to achieve efficient and stable PSCs.

Bone marrow CD8+ Trm cells induced by IL-15 and CD16+ monocytes contribute to HSPC destruction in human severe aplastic anemia.

Idiopathic severe aplastic anemia (SAA) is a disease of bone marrow failure caused by T-cell-induced destruction of hematopoietic stem and progenitor cells (HSPCs), however the mechanism remains unclear. We performed single-cell RNA sequencing of PBMCs and BMMCs from SAA patients and healthy donors and identified a CD8+ T cell subset with a tissue residency phenotype (Trm) in bone marrow that exhibit high IFN-γ and FasL expression and have a higher ability to induce apoptosis in HSPCs in vitro through FasL expression. CD8+ Trm cells were induced by IL-15 presented by IL-15Rα on monocytes, especially CD16+ monocytes, which were increased in SAA patients. CD16+ monocytes contributed to IL-15-induced CD38+CXCR6+ pre-Trm differentiation into CD8+ Trm cells, which can be inhibited by the CD38 inhibitor 78c. Our results demonstrate that IL-15-induced CD8+ Trm cells are pathogenic cells that mediate HSPC destruction in SAA patients and are therapeutic targets for future treatments.

Current status and new experimental diagnostic methods of invasive fungal infections after hematopoietic stem cell transplantation.

Invasive fungal infections (IFIs) are common and life-threatening complications in post-hematopoietic stem cell transplantation (post-HSCT) recipients, Severe IFIs can lead to systemic infection and organ damage, which results in high mortality in HSCT recipients. With the development of the field of fungal infection diagnosis, more and more advanced non-culture diagnostic tools have been developed, such as glip biosensors, metagenomic next-generation sequencing, Magnetic Nanoparticles and Identified Using SERS via AgNPs+ , and artificial intelligence-assisted diagnosis. The advanced diagnostic approaches contribute to the success of HSCT and improve the overall survival of post-HSCT leukemia patients by supporting therapeutical decisions. This review provides an overview of the characteristics of two high-incidence IFIs in post-HSCT recipients and discusses some of the recently developed IFI detection technologies. Additionally, it explores the potential application of cationic conjugated polymer fluorescence resonance energy transfer (CCP-FRET) technology for IFI detection. The aim is to offer insights into selecting appropriate IFI detection methods and gaining an understanding of novel fungal diagnostic approaches in laboratory settings.

Acid tolerance response of Salmonella during the squid storage and its amine production capacity analysis.

Salmonella exhibits a strong inducible acid tolerance response (ATR) under weak acid conditions, and can also induce high-risk strains that are highly toxic, acid resistant, and osmotic pressure resistant to aquatic products. However, the induction mechanism is not yet clear. Therefore, this study aims to simulate the slightly acidic, low-temperature, and high-protein environment during squid processing and storage. Through λRed gene knockout, exploring the effects of low-acid induction, long-term low-temperature storage, and two-component regulation on Salmonella ATR. In this study, we found the two-component system, PhoP/PhoQ and PmrA/PmrB in Salmonella regulates the amino acid metabolism system and improves bacterial acid tolerance by controlling arginine and lysine. Compared with the two indicators of total biogenic amine and diamine content, biogenic amine index and quality index were more suitable for evaluating the quality of aquatic products. The result showed that low-temperature treatment could inhibit Salmonella-induced ATR, which further explained the ATR mechanism from the amino acid metabolism.

Mitotic waves in frog egg extracts: Transition from phase waves to trigger waves.

Cyclin-dependent kinase 1 (Cdk1) activity rises and falls throughout the cell cycle, a cell-autonomous process known as mitotic oscillations. These oscillators can synchronize when spatially coupled, providing a crucial foundation for rapid synchronous divisions in large early embryos like Drosophila (~ 0.5 mm) and Xenopus (~ 1.2 mm). While diffusion alone cannot achieve such long-range coordination, recent studies have proposed two types of mitotic waves, phase and trigger waves, to explain the phenomena. How the waves establish over time for efficient spatial coordination remains unclear. Using Xenopus laevis egg extracts and a Cdk1 FRET sensor, we observe a transition from phase waves to a trigger wave regime in an initially homogeneous cytosol. Adding nuclei accelerates such transition. Moreover, the system transitions almost immediately to this regime when externally driven by metaphase-arrested extracts from the boundary. Employing computational modeling, we pinpoint how wave nature, including speed-period relation, depends on transient dynamics and oscillator properties, suggesting that phase waves appear transiently due to the time required for trigger waves to entrain the system and that spatial heterogeneity promotes entrainment. Therefore, we show that both waves belong to a single biological process capable of coordinating the cell cycle over long distances.

Comparing the effects of empagliflozin and liraglutide on lipid metabolism and intestinal microflora in diabetic mice.

Background and Objectives: Recent studies have shown that the imbalance of intestinal flora is related to the occurrence and progression of diabetic nephropathy (DN) and can affect lipid metabolism. Sodium-dependent glucose transporters 2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist are commonly used hypoglycemic drugs and have excellent renal safety. The purpose of this study was to compare the protective effects of empagliflozin and liraglutide on kidneys, lipid metabolism, and intestinal microbiota in diabetic mice. Methods: We established a mouse model of type two diabetes by feeding rats a high-fat diet (HFD) followed by an intraperitoneal injection of STZ. The mice were randomly divided into groups: normal control (NC), diabetic model (DM), liraglutide treatment (LirT), empagliflozin treatment (EmpT), and liraglutide combined with empagliflozin treatment (Emp&LirT) groups. Blood glucose, lipids, creatinine, and uric acid, as well as urinary nitrogen and albumin levels were measured. The renal tissues were subjected to HE, PAS and Masson's staining. These parameters were used to evaluate renal function and histopathological changes in mice. Mice feces were also collected for 16sRNA sequencing to analyze the composition of the intestinal flora. Results: All the indexes related to renal function were significantly improved after treatment with drugs. With respect to lipid metabolism, both drugs significantly decreased the serum triglyceride levels in diabetic mice, but the effect of liraglutide on reducing serum cholesterol was better than that of empagliflozin. However, empagliflozin had a better effect on the reduction of low-density lipoproteins (LDL). The two drugs had different effects on intestinal flora. At the phylum level, empagliflozin significantly reduced the ratio of Firmicutes to Bacteroidota, but no effect was seen with liraglutide. At the genus level, both of them decreased the number of Helicobacter and increased the number of Lactobacillus. Empagliflozin also significantly increased the abundance of Muribaculaceae, Muribaculum, Olsenella, and Odoribacter, while liraglutide significantly increased that of Ruminococcus. Conclusion: Liraglutide and empagliflozin were both able to improve diabetes-related renal injury. However, the ability of empagliflozin to reduce LDL was better compared to liraglutide. In addition, their effects on the intestine bacterial flora were significantly different.

Diagnosis of pulmonary hemorrhagic leptospirosis complicated by invasive pulmonary aspergillosis complemented by metagenomic next-generation sequencing: a case report.

Background: Leptospirosis is a bacterial zoonosis with variable clinical manifestations. Pulmonary diffuse hemorrhagic leptospirosis often occurs rapidly and, when not promptly diagnosed and treated, it can be life-threatening. Aspergillus flavus is an opportunistic fungus that is commonly seen in immunosuppressed patients. Invasive pulmonary aspergillosis also progresses rapidly. This case study describes a patient with severe pneumonia caused by pulmonary hemorrhagic leptospirosis combined with invasive pulmonary aspergillosis. We have found almost no clinical reports to date on these two diseases occurring in the same patient. Case presentation: A 73-year-old male arrived at our hospital complaining of fever, general malaise, and hemoptysis that had lasted 4 days. The patient was initially diagnosed with severe pneumonia in the emergency department, but he did not respond well to empiric antibiotics. Subsequently, the patient's condition worsened and was transferred to the ICU ward after emergency tracheal intubation and invasive ventilator. In the ICU, antibacterial drugs were adjusted to treat bacteria and fungi extensively. Although the inflammatory indices decreased, the patient still had recurrent fever, and a series of etiological tests were negative. Finally, metagenomic next-generation sequencing (mNGS) of bronchial alveolar lavage fluid detected Leptospira interrogans and Aspergillus flavus. After targeted treatment with penicillin G and voriconazole, the patient's condition improved rapidly, and he was eventually transferred out of the ICU and recovered. Conclusion: Early recognition and diagnosis of leptospirosis is difficult, especially when a patient is co-infected with other pathogens. The use of mNGS to detect pathogens in bronchial alveolar lavage fluid is conducive to early diagnosis and treatment of the disease, and may significantly improve the prognosis in severe cases.