The ldh Gene Plays a Crucial Role in Mediating the Pathogen Control of Lactiplantibacillus plantarum AR113.

Effectively managing foodborne pathogens is imperative in food processing, where probiotics play a crucial role in pathogen control. This study focuses on the Lactiplantibacillus plantarum AR113 and its gene knockout strains, exploring their antimicrobial properties against Escherichia coli O157:H7 and Staphylococcus aureus. Antimicrobial assays revealed that the inhibitory effect of AR113 increases with its growth and the potential bacteriostatic substance is acidic. AR113Δldh, surpassed AR113Δ0273&2024, exhibited a complete absence of bacteriostatic properties, which indicates that lactic acid is more essential than acetic acid in the bacteriostatic effect of AR113. However, the exogenous acid validation test affirmed the equivalent superior bacteriostatic effect of lactic acid and acetic acid. Notably, AR113 has high lactate production and deletion of the ldh gene not only lacks lactate production but also affects acetic production. This underscores the ldh gene's pivotal role in the antimicrobial activity of AR113. In addition, among all the selected knockout strains, AR113ΔtagO and ΔccpA also had lower antimicrobial effects, suggesting the importance of tagO and ccpA genes of AR113 in pathogen control. This study contributes insights into the antimicrobial potential of AR113 and stands as the pioneering effort to use knockout strains for comprehensive bacteriostatic investigations.

Inflammation assessment and therapeutic monitoring based on highly sensitive and multi-level electrochemical detection of PGE2.

Prostaglandin E2 (PGE2), an eicosane, regulates the physiological activity of inflammatory cells and represents a potential therapeutic target for facilitating tissue repair in vivo. In our work, an electrochemical immunosensor employing Ketjen black-Au nanoparticles (KB-Au) and poly tannic acid nanospheres conjugated with anti-PGE2 polyclonal antibody (PTAN-Ab) was designed to ultra-sensitively analyze PGE2 levels secreted by living cells and tissues. Antibody assembly strategies were explored to achieve signal amplification. Moreover, we studied the therapy effects of docosahexaenoic acid (DHA), arachidonic acid (AA), hyaluronic acid (HA), and small molecule 15-hydroxyprostaglandin dehydrogenase inhibitor (SW033291) on inflammation and evaluated the protective functions of HA and SW033291 in a murine model subjected to colitis induced by dextran sulfate sodium (DSS) using the developed sensor. The sensor exhibited a linear range of 10-5-106 fg/mL and a detection limit (LOD) of 10-5 fg/mL. Fetal bovine serum (FBS) samples were used to achieve high recovery of target analytes. This study not only presents an effective strategy for ultra-sensitively monitoring PGE2 but also provides valuable insights into assessing the degree of inflammation and the therapeutic effect of related drugs. Research on human health monitoring and regenerative medicine could greatly benefit from the findings.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

Design, synthesis and structure-activity relationships of novel non-ketolides: 9-Oxime clarithromycin featured with seven-to thirteen-atom-length diamine linkers at 3-OH.

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.

Sleep, physical activity, and sedentary behaviors in relation to overall cancer and site-specific cancer risk: A prospective cohort study.

Large prospective studies are required to better elucidate the associations of physical activity, sedentary behaviors (SBs), and sleep with overall cancer and site-specific cancer risk, accounting for the interactions with genetic predisposition. The study included 360,271 individuals in UK Biobank. After a median follow-up of 12.52 years, we found higher total physical activity (TPA) level and higher sleep scores were related to reduced risk of cancer while higher SB level showed a positive association with cancer. Compared with high TPA-healthy sleep group and low SB-healthy sleep group, low TPA-poor sleep group and high SB-poor sleep group had the highest risk for overall cancer, breast cancer, and lung cancer. Adherence to a more active exercise pattern was associated with a lower risk of cancer irrespective of genetic risk. Our study suggests that improving the quality of sleep and developing physical activity habits might yield benefits in mitigating the cancer risk.

[Ce3+-OV-Ce4+] Located Surface-Distributed Sheet Cu-Zn-Ce Catalysts for Methanol Production by CO2 Hydrogenation.

The metal-support interaction is crucial for the performance of Cu-based catalysts. However, the distinctive properties of the support metal element itself are often overlooked in catalyst design. In this paper, a sheet Cu-Zn-Ce with [Ce3+-OV-Ce4+] located on the surface was designed by the sol-gel method. Through EPR and X-ray photoelectron spectroscopy (XPS), the relationship between the content of oxygen vacancies and Ce was revealed. Ce itself induces the generation of [Ce3+-OV-Ce4+]. Through ICP-MS, XPS, and SEM-mapping, the Ce-induced formation of [Ce3+-OV-Ce4+] located on the catalyst surface was demonstrated. CO2-TPD and DFT calculations further revealed that [Ce3+-OV-Ce4+] enhanced CO2 adsorption, leading to a 10% increase in methanol selectivity compared to Cu-Zn-Ce synthesized via the coprecipitation method.

Comparison of CRISPR typing and conventional molecular methods for distinguishing Laribacter hongkongensis isolates from fish, frogs and humans.

High-resolution and efficient typing for Laribacter hongkongensis (L. hongkongensis) is essential for epidemiological investigation of such emerging foodborne pathogens. Clustered regularly interspaced short palindromic repeats (CRISPR) typing is an innovative molecular method that shows great promise for L. hongkongensis typing. Here, we explored the CRISPR typing method by combining CRISPR1 and CRISPR2 loci to characterize a collection of 109 L. hongkongensis isolates from humans and animals and compared it to current molecular methods such as pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The results showed that all three methods have high discriminatory power (diversity index was 0.9902 for PFGE, 0.9663 for CRISPR and 0.9562 for MLST); strong congruence was observed between them (Rand index was 0.969 between CRISPR and PFGE, 0.953 between CRISPR and MLST, 0.958 between PFGE and MLST). CRISPR typing could well distinguish the isolates in the same STs or PFGE profiles, and the genetic information contained by the CRISPR array is useful for deep phylogenetic typing. We demonstrate that rapid CRISPR typing is a practical genetic fingerprinting tool with high resolution, comparable ease of use and lower cost, ability to track the source of various groups of L. hongkongensis strains and indication of genetic characteristics.

Stabilizing axin leads to optic nerve hypoplasia in a mouse model of autism.

Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.

Odor Fingerprinting of Chitosan and Source Identification of Commercial Chitosan: HS-GC-IMS, Multivariate Statistical Analysis, and Tracing Path Study.

Chitosan samples were prepared from the shells of marine animals (crab and shrimp) and the cell walls of fungi (agaricus bisporus and aspergillus niger). Fourier-transform infrared spectroscopy (FT-IR) was used to detect their molecular structures, while headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) was employed to analyze their odor composition. A total of 220 volatile organic compounds (VOCs), including esters, ketones, aldehydes, etc., were identified as the odor fingerprinting components of chitosan for the first time. A principal component analysis (PCA) revealed that chitosan could be effectively identified and classified based on its characteristic VOCs. The sum of the first three principal components explained 87% of the total variance in original information. An orthogonal partial least squares discrimination analysis (OPLS-DA) model was established for tracing and source identification purposes, demonstrating excellent performance with fitting indices R2X = 0.866, R2Y = 0.996, Q2 = 0.989 for independent variable fitting and model prediction accuracy, respectively. By utilizing OPLS-DA modeling along with a heatmap-based tracing path study, it was found that 29 VOCs significantly contributed to marine chitosan at a significance level of VIP > 1.00 (p < 0.05), whereas another set of 20 VOCs specifically associated with fungi chitosan exhibited notable contributions to its odor profile. These findings present a novel method for identifying commercial chitosan sources, which can be applied to ensure biological safety in practical applications.

Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection.

Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.

Whole-exome sequencing of individuals from an isolated population under extreme conditions implicates rare risk variants of schizophrenia.

Schizophrenia (SCZ), which affects approximately 1% of the world's population, is a global public health concern. It is generally considered that the interplay between genes and the environment is important in the onset and/or development of SCZ. Although several whole-exome sequencing studies have revealed rare risk variants of SCZ, no rare coding variants have been strongly replicated. Assessing isolated populations under extreme conditions might lead to the discovery of variants with a recent origin, which are more likely to have a higher frequency than chance to reflect gene-environment interactions. Following this approach, we examined a unique cohort of Tibetans living at an average altitude above 4500 meters. Whole-exome sequencing of 47 SCZ cases and 53 controls revealed 275 potential novel risk variants and two known variants (12:46244485: A/G and 22:18905934: A/G) associated with SCZ that were found in existing databases. Only one gene (C5orf42) in the gene-based statistics surpassed the exome-wide significance in the cohort. Metascape enrichment analysis suggested that novel risk genes were strongly enriched in pathways relevant to hypoxia, neurodevelopment, and neurotransmission. Additionally, 47 new risk genes were followed up in Han sample of 279 patients with SCZ and 95 controls, only BAI2 variant appearing in one case. Our findings suggest that SCZ patients living at high altitudes may have a unique risk gene signature, which may provide additional information on the underlying biology of SCZ, which can be exploited to identify individuals at greater risk of exposure to hypoxia.

Enhancing CO2 storage and marine carbon sink based on seawater mineral carbonation.

Human activities emitting carbon dioxide (CO2) have caused severe greenhouse effects and accelerated climate change, making carbon neutrality urgent. Seawater mineral carbonation technology offers a promising negative emission strategy. This work investigates current advancements in proposed seawater mineral carbonation technologies, including CO2 storage and ocean chemical carbon sequestration. CO2 storage technology relies on indirect mineral carbonation to fix CO2, involving CO2 dissolution, Ca/Mg extraction, and carbonate precipitation, optimized by adding alkaline substances or using electrochemical methods. Ocean chemical carbon sequestration uses natural seawater for direct mineral carbonation, enhanced by adding specific materials to promote carbonate precipitation and increase CO2 absorption, thus enhancing marine carbon sinks. This study evaluates these technologies' advantages and challenges, including reaction rates, costs, and ecological impacts, and analyzes representative materials' carbon fixation potential. Literature indicates that seawater mineral carbonation can play a significant role in CO2 storage and enhancing marine carbon sinks in the coming decades.

Exosomal membrane proteins analysis using a silicon nanowire field effect transistor biosensor.

Exosomes are of great significance in clinical diagnosis, due to their high homology with parental generation, which can reflect the pathophysiological status. However, the quantitative and classification detection of exosomes is still faced with the challenges of low sensitivity and complex operation. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a Silicon nanowire field effect transistor biosensor (Si-NW Bio-FET). First, the impact of Debye length on Si-NW Bio-FET detection was investigated through simulation. The simulation results demonstrated that as the Debye length increased, the electrical response to Si-NW produced by charged particle at a certain distance from the surface of Si-NW was greater. A Si-NW Bio-FET modified with specific antibody CD81 on the nanowire was fabricated then used for detection of cell line-derived exosomes, which achieved a low limit of detection (LOD) of 1078 particles/mL in 0.01 × PBS. Furthermore, the Si-NW Bio-FETs modified with specific antibody CD9, CD81 and CD63 respectively, were employed to distinguish exosomes derived from human promyelocytic leukemia (HL-60) cell line in three different states (control group, lipopolysaccharide (LPS) inflammation group, and LPS + Romidepsin (FK228) drug treatment group), which was consistent with nano-flow cytometry. This study provides a highly sensitive method of directly quantifying exosomes without labeling, indicating its potential as a tool for disease surveillance and medication instruction.

Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

Vaginal microbiome dysbiosis as a novel noninvasive biomarker for detection of chronic endometritis in infertile women.

OBJECTIVE: To identify the vaginal microbial signature in women with chronic endometritis (CE) and investigate the potential of vaginal microbiome characterization as a novel diagnostic tools for CE. METHODS: A cross-sectional study was conducted to compare the characteristics of the vaginal microbiome in 98 women who underwent endometrial biopsy for routine clinical inspection of infertility (49 women diagnosed with CE and 49 with non-CE). The vaginal microbiome was analyzed using 16S ribosomal RNA gene amplicon sequencing. The study included an analysis of diversity, bacterial abundance, and microbial function. In addition, microbial markers were identified, and a CE classifier was developed. RESULTS: The relative abundances of genera, including Bifidobacterium, Prevotella and Gardnerella, were found to be different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways reported differential expression in metabolism-related pathways in the two groups. We identified four microbial markers of CE (Enterobacter, Prevotella, Faecalibacterium, and Phascolarctobacterium) and developed a predictive classifier for diagnosing CE, achieving an area under the curve of 83.26%. CONCLUSION: The results of the current study revealed that, compared with the non-CE controls, patients with CE have a different vaginal microbiota, highlighting the diagnostic significance of the vaginal microbiome as a promising noninvasive biomarker in detecting CE.