Fighting against Clostridioides difficile infection: Current medications.

Clostridioides difficile (formerly Clostridium difficile) has been regarded as an "urgent threat" and a significant global health problem, as life-threatening diarrhea and refractory recurrence are common in patients with C. difficile infection (CDI). Unfortunately, the available anti-CDI drugs are limited. Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and fecal microbiota transplantation (FMT) for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g., teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g., Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g., vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g., Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarizes current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation.

The influence of progeny-Parents family travel on the well-being of the elderly in filial piety culture.

Grounded in the cultural context of Chinese filial piety, this study employs structural equation model to analyze survey data from elderly participants. It explores the effect and path of progeny-parents family travel on the elderly's sense of well-being and examines the mediating roles of generational interaction, optimistic emotion, and psychological resilience. The findings indicate that progeny-parents family travel positively influences the well-being of the elderly, with generational interaction, optimistic emotion, and psychological resilience serving as intermediary roles. Theoretically, this study enriches the localized perspective of family travel's psychological and behavioral impact on the elderly. It elucidates the spillover effects of family travel within the framework of filial piety culture, delineates the mechanisms by which family travel enhances elderly well-being, and offers theoretical insights for businesses to develop customized family travel products and services.

Rapid in-situ aerobic biodegradation of high salt and oily food waste employing constructed synthetic microbiome.

The high salt content of food waste (FW) severely limits microbial physiological activity and reduces its biodegradability. In this study, a salt-tolerant thermophilic bacterial agent that consists of four different substrate degradation functional strains was evaluated for efficient high salt and oily FW in solid-state aerobic biodegradation disposers. The phy-chemical properties, enzyme activities, microbial community structure, and function during the biodegradation process were evaluated under high salt (5%) stress. The results showed that the agent promoted the degradation rate, increased the matrix temperature, decreased the moisture content (MC), and enhanced enzyme activities without putrid smell. High-throughput sequencing indicated community structure succession between different groups and the positive contribution of the inoculated functional strains. During the FW biodegradation process, the Bacillus sp. inoculated was the dominant genus in the agent group. Furthermore, CCA further confirmed the positive effects of the four inoculated strains on high salt and oily FW aerobic biodegradation. Functional prediction and metabolite results both confirmed that the agent was more efficient in carbon, amino acid, and lipid metabolism, which demonstrated that the synthetic microbial consortium holds a potential advantage for efficiency and subsequent resource utilization for organic fertilizer.

Effects of nitrogen regulation on heavy metal phytoextraction efficiency (Leucaena leucocephala): application of a nitrogen fertilizer and a fungal agent.

Lead (Pb) and cadmium (Cd) have been identified as the primary contaminants in soil, posing potential health threats. This study aimed to examine the effects of applying a nitrogen fertilizer and a fungal agent Trichoderma harzianum J2 (nitrogen alone, fungi alone, and combined use) on the phytoremediation of soils co-contaminated with Pb and Cd. The growth of Leucaena leucocephala was monitored in the seedling, differentiation, and maturity stages to fully comprehend the remediation mechanisms. In the maturity stage, the biomass of L. leucocephala significantly increased by 18% and 29% under nitrogen-alone (NCK+) and fungal agent-alone treatments (J2), respectively, compared with the control in contaminated soil (CK+). The remediation factors of Pb and Cd with NCK+ treatment significantly increased by 50% and 125%, respectively, while those with J2 treatment increased by 73% and 145%, respectively. The partial least squares path model suggested that the nitrogen-related soil properties were prominent factors affecting phytoextraction compared with biotic factors (microbial diversity and plant growth). This model explained 2.56 of the variation in Cd concentration under J2 treatment, and 2.97 and 2.82 of the variation in Pb concentration under NCK+ and J2 treatments, respectively. The redundancy analysis showed that the samples under NCK+ and J2 treatments were clustered similarly in all growth stages. Also, Chytridiomycota, Mucoromucota, and Ciliophora were the key bioindicators for coping with heavy metals. Overall, a similar remediation mechanism allowed T. harzianum J2 to replace the nitrogen fertilizer to avoid secondary pollution. In addition, their combined use further increased the remediation efficiency.

Facile construction of a stable core-shell spherically magnetic polyimide covalent organic framework for efficient extraction of phenylurea herbicides.

Efficient enrichment is crucial for the highly sensitive monitoring of phenylurea herbicides (PUHs) in various environmental waters. In this work, a stable core-shell spherically magnetic polyimide covalent organic framework (COF) was synthesized via a simple template-mediated precipitation polymerization method under mild conditions using tri(4-aminophenyl)amine (TAPA) and 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA) as the building units (denoted as Fe3O4@TAPA-BPDA). The Fe3O4@TAPA-BPDA exhibits remarkable adsorption performance for PUHs with an optimized adsorption time of only 10 min. The adsorption of PUHs by Fe3O4@TAPA-BPDA followed the pseudo-second-order kinetic model and the Langmuir model. Furthermore, hydrogen bonding, halogen bonding, hydrophobic interaction, electro donor-acceptor interaction and π-π interactions are identified as the dominant mechanisms contributing to excellent adsorption performance. It was demonstrated that halogen bonds play an important role in the adsorption of substances containing chlorine atoms. The Fe3O4@TAPA-BPDA is easy to operate and highly regenerable. A simple magnetic solid-phase extraction (MSPE) method based on the Fe3O4@TAPA-BPDA was then developed for the rapid extraction of five PUHs in real samples, coupled with high-performance liquid chromatography (HPLC) determination. The analytical method developed has a linear range of 0.5-50 ng/mL, and the limit of detection (LOD) ranges from 0.06 to 0.10 ng/mL. The method exhibits good accuracy with recoveries ranged from 74.5 % to 111.4 %. The analytical method was successfully applied to the highly sensitive detection of PUHs in environmental water samples, which highlighting the potential application of the Fe3O4@TAPA-BPDA in the sample pretreatment.

Genome-wide identification, expression analysis, and abiotic stress response of the CBL and CIPK gene families in Artocarpus nanchuanensis.

Artocarpus nanchuanensis, the northernmost species in the jackfruit genus, has great economic and horticultural value due to its nutritious fruit and beautiful tree shape. Calcineurin B-like proteins (CBLs) act as plant-specific Ca2+ sensors and participate in regulating plant responses to various abiotic stresses by interacting with CBL-interacting protein kinases (CIPKs). However, the characteristics and functions of the CBL and CIPK genes in A. nanchuanensis are still unclear. Here, we identified 14 CBL and 33 CIPK genes from the A. nanchuanensis genome, and based on phylogenetic analysis, they were divided into 4 and 7 clades, respectively. Gene structure and motif analysis indicated that the AnCBL and AnCIPK genes were relatively conserved. Colinear analysis showed that segmental duplication contributed to the expansion of the AnCBL and AnCIPK gene families. Expression analysis showed that AnCBL and AnCIPK genes were widely expressed in various tissues of A. nanchuanensis and exhibited tissue-specific expression. In addition, three genes (AnCBL6, AnCIPK7/8) may play important roles in response to salt, cold, and drought stresses. In summary, this study lays an important foundation for the improvement of stress resistance in A. nanchuanensis and provides new insight for the functional research on CBL and CIPK gene families.

The Associations of Physical Activity and Health-Risk Behaviors toward Depressive Symptoms among College Students: Gender and Obesity Disparities.

Engaging in health-risk behaviors (HRBs) may be correlated with depressive symptoms among college students, but these relationships require more research. The purpose of this study was to examine the associations of physical activity levels (i.e., light [LPA] and moderate-vigorous [MVPA]) and HRBs (i.e., sedentary behavior [screen-based and non-screen-based behavior] and cigarette and e-cigarette tobacco use) with depressive symptoms in a sample of college students. Physical activity levels and HRBs were assessed through validated questionnaires. In total, 366 students participated (Mage = 22.59 ± 3.54; 60.1% female; 52.9% normal weight). E-cigarette use in males (ß = 0.23, p < 0.05) and screen-based sedentary behavior in females (ß = 0.14, p < 0.05) showed significant predictive utility toward depressive symptoms. In the overweight/obese group, screen-based sedentary behaviors (ß = 0.19, p < 0.05) and e-cigarette use (ß = 0.23, p < 0.01) showed significant predictive utility toward depressive symptoms. Females reported higher levels of depressive symptoms (Mfemale = 18.23 vs. Mmale = 14.81; η2 = 0.03) and less MVPA (Mmale = 52.83 vs. Mfemale = 41.09; η2 = 0.06) than males. Enhancing mental health by improving physical activity and eliminating HRBs should be tailored toward at-risk demographics.

UBE2L3 expression in human gastric cancer and its clinical significance.

PURPOSE: Gastric cancer (GC) is prevalent as one of the most common malignant tumors globally, with a particularly high incidence in China. The role of UBE2L3 in the initiation and progression of various cancers has been well documented, but its specific significance in GC is not yet fully elucidated. The objective of this study is to examine the expression and importance of UBE2L3 in human gastric cancer tissues. METHODS: Immunohistochemical staining and survival analysis were conducted on 125 cases of GC. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to assess the expression of UBE2L3 in GC cell lines. Cell lines with UBE2L3 knockdown and overexpression were cultured through lentivirus transfection and subsequently assessed using Western blot analysis. The involvement of UBE2L3 in the proliferation, invasion, and apoptosis of GC cells was confirmed through in vitro experiments, and its capacity to facilitate tumor growth was also validated in in vivo studies. RESULTS: The up-regulation of UBE2L3 expression was observed in GC, and its high expression was found to be significantly associated with the degree of differentiation (χ2 = 6.153, P = 0.0131), TNM stage (χ2 = 6.216, P = 0.0447), and poor overall survival. In vitro, UBE2L3 has been shown to enhance functions in GC cell lines, such as promoting proliferation and invasion, and inhibiting apoptosis. In vivo experiments have validated the role of UBE2L3 in promoting tumor growth. CONCLUSIONS: The findings of our study demonstrate the significant involvement of UBE2L3 in the pathogenesis and advancement of gastric cancer, suggesting its potential as a therapeutic target.

High expression of NOTCH2 in gastric adenocarcinoma: A novel early diagnostic target.

BACKGROUND AND AIM: NOTCH2 is overexpressed in gastric cancer (GC), and its enhanced activity is significantly correlated with worse tumor characteristics. We aim to analyze the clinicopathologic correlation between NOTCH2 and the molecular typing of GC by immunohistochemistry and by transcriptional sequencing. METHODS: In this immunohistochemical study, we detected NOTCH2, EBER, P53, HER2, MLH1, MSH2, PMS2, and MSH6 and evaluated the association of NOTCH2 with clinical and histopathological features in a large single-institutional series of gastric adenocarcinomas (n = 488). The correlation was also investigated between immunohistochemical results and survival outcomes. RESULTS: High NOTCH2 expression (2+/3+) was found in 139/488 (27.5%) samples analyzed. NOTCH2 expression was correlated with early stage T1 (P < 0.0001), GC in the fundus (P = 0.0364), and positive P53 status (P = 0.0019). We did not find an association between NOTCH2 and HER2, microsatellite instability, EBER, and overall survival. Through RNA sequencing, it was revealed that NOTCH2 plays an important biological function in the pathogenesis and development of GC. CONCLUSIONS: Our findings suggested that NOTCH2 may be a potential diagnostic target for GC due to the fact that its high expression is closely associated with the early stages of cancer.

Application of propofol-remifentanil intravenous general anesthesia combined with regional block in pediatric ophthalmic surgery.

OBJECTIVE: The aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery. METHODS: A total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups. RESULTS: All the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05). CONCLUSION: Propofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.

Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis.

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.

Emerging Trends in Magnetic Resonance Fingerprinting for Quantitative Biomedical Imaging Applications: A Review.

Magnetic resonance imaging (MRI) stands as a vital medical imaging technique, renowned for its ability to offer high-resolution images of the human body with remarkable soft-tissue contrast. This enables healthcare professionals to gain valuable insights into various aspects of the human body, including morphology, structural integrity, and physiological processes. Quantitative imaging provides compositional measurements of the human body, but, currently, either it takes a long scan time or is limited to low spatial resolutions. Undersampled k-space data acquisitions have significantly helped to reduce MRI scan time, while compressed sensing (CS) and deep learning (DL) reconstructions have mitigated the associated undersampling artifacts. Alternatively, magnetic resonance fingerprinting (MRF) provides an efficient and versatile framework to acquire and quantify multiple tissue properties simultaneously from a single fast MRI scan. The MRF framework involves four key aspects: (1) pulse sequence design; (2) rapid (undersampled) data acquisition; (3) encoding of tissue properties in MR signal evolutions or fingerprints; and (4) simultaneous recovery of multiple quantitative spatial maps. This paper provides an extensive literature review of the MRF framework, addressing the trends associated with these four key aspects. There are specific challenges in MRF for all ranges of magnetic field strengths and all body parts, which can present opportunities for further investigation. We aim to review the best practices in each key aspect of MRF, as well as for different applications, such as cardiac, brain, and musculoskeletal imaging, among others. A comprehensive review of these applications will enable us to assess future trends and their implications for the translation of MRF into these biomedical imaging applications.

Mamestra brassicae Multiple Nucleopolyhedroviruses Prevents Pupation of Helicoverpa armigera by Regulating Juvenile Hormone Titer.

Baculovirus infection can prevent the pupation of insects. Juvenile hormone (JH) plays a vital role in regulating insect molting and metamorphosis. However, the molecular mechanism of baculovirus preventing the pupation of larvae by regulating the Juvenile hormone (JH) pathway is still unclear. In this study, we found that the Mamestra brassicae multiple nucleopolyhedroviruses (MbMNPV) infection prolonged the larval stage of fourth instar Helicoverpa armigera (H. armigera) by 0.52 d and caused an increase in JH titer. To identify the genes that contribute to the JH increase in H. armigera-MbMNPV interaction, we analyzed mRNA expression profiles of the fat bodies of H. armigera infected by MbMNPV. A total of 3637 differentially expressed mRNAs (DE-mRNAs) were filtered out through RNA-seq analysis. These DE-mRNAs were mainly enriched in Spliceosome, Ribosome biogenesis in eukaryotes, Aminoacyl-tRNA biosynthesis, Mismatch repair, and RNA degradation signaling pathway, which are related to the virus infection. Real-time PCR was used to verify the RNA sequencing results. To find out which genes caused the increase in JH titer, we analyzed all the DE-mRNAs in the transcriptome and found that the JHE and JHEH genes, which were related to JH degradation pathway, were down-regulated. JHE and JHEH genes in the larvae of MbMNPV-infected group were significantly down-regulated compared with the control group by RT-qPCR. We further proved that the JH is degraded by JHE in H. armigera larvae by RNAi, ELISA, RT-qPCR and bioassay, while the hydrolysis of JH by JHEH in H. armigera larvae can almost be ignored. Knocking down of HaJHE promoted the expression of the JH receptor gene Met and the downstream gene Kr-h1, and the replication of MbMNPV. This study clarified that JH is mainly degraded by JHE in H. armigera larvae. The MbMNPV infection of H. armigera larvae leads to the increase of JH titer by inhibiting the expression of JHE. The increase in JH titer promotes the expression of the JH receptor gene Met and the downstream gene Kr-h1, which prevents the pupation of H. armigera, and promotes MbMNPV replication. This study provides new insights into H. armigera and MbMNPV interaction mechanisms.

The first reported pulmonary nocardiosis caused by Nocardia gipuzkoensis resisted to TMP-SMZ in an immunocompetent patient.

BACKGROUND: . Nocardia gipuzkoensis was first described as a novel and distinct species in 2020 by Imen Nouioui and pulmonary nocardiosis associated with Nocardia gipuzkoensis was once reported in two bronchiectasis patients. Noteworthy, both reported Nocardia gipuzkoensis cases showed sensitivity to Trimethoprim/Sulfamethoxazol (TMP-SMZ), which are usually recommended for empirical therapy. METHODS: We reported the third case of Nocardia gipuzkoensis infection in a 16-year-old girl with chief complaints of cough, persistent chest and back pain. No underlying immuno-suppressive conditions and glucocorticoid use was revealed. Patchy lesions next to spine and located in the posterior basal segment of lower lobes of left lung were seen in thorax computed tomography (CT), but no pathogenic bacteria was detected according to routine laboratory testings. RESULTS: Metagenomic next-generation sequencing (mNGS) combined with Whole Genome Sequencing (WGS) was used to classified our isolate from bronchoalveolar lavage fluid (BALF) as a Nocardia gipuzkoensis. It is worth mentioning that drug susceptibility testing of our isolate showed resistance to TMP-SMZ, which was never reported before. The patient improved remarkably both clinically and radiographically according to the treatment with Imipenem-cilastatin infusion alone. CONCLUSION: mNGS and WGS showed excellent performance in identifying Nocardia genus to the species level and improving detection rate of Nocardia gipuzkoensis ignored by traditional culture. Different from previously reported cases, Nocardia gipuzkoensis infection case showed resistance to TMP-SMZ, which is an unprecedented finding and a crucial addition to our understanding of the antibacterial spectrum of Nocardia gipuzkoensis. The successful treatment with Imipenem-cilastatin infusion alone in this case is a testament to the importance of precise identification and tailored antibiotic therapy.

Ciceribacter sichuanensis sp. nov., a plant growth promoting rhizobacterium isolated from root nodules of soybean in Sichuan, China.

The fast-growing rhizobia-like strains S101T and S153, isolated from root nodules of soybean (Glycine max) in Sichuan, People's Republic of China, underwent characterization using a polyphasic taxonomy approach. The strains exhibited growth at 20-40 °C (optimum, 28 °C), pH 4.0-10.0 (optimum, pH 7.0) and up to 2.0% (w/v) NaCl (optimum, 0.01%) on Yeast Mannitol Agar plates. The 16S rRNA gene of strain S101T showed 98.4% sequence similarity to the closest type strain, Ciceribacter daejeonense L61T. Major cellular fatty acids in strain S101T included summed feature 8 (C18:1ω7c and/or C18:1ω6c) and C19:0 cyclo ω8c. The predominant quinone was ubiquinone-10. The polar lipids of strain S101T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmethyl ethanolamine, phosphatidyl ethanolamine, amino phospholipid, unidentified phosphoglycolipid and unidentified amino-containing lipids. The DNA G + C contents of S101T and S153 were 61.1 and 61.3 mol%, respectively. Digital DNA-DNA hybridization relatedness and average nucleotide identity values between S101T and C. daejeonense L61T were 46.2% and 91.4-92.2%, respectively. In addition, strain S101T promoted the growth of soybean and carried nitrogen fixation genes in its genome, hinting at potential applications in sustainable agriculture. We propose that strains S101T and S153 represent a novel species, named Ciceribacter sichuanensis sp. nov., with strain S101T as the type strain (= CGMCC 1.61309 T = JCM 35649 T).

Butyrate alleviates alcoholic liver disease-associated inflammation through macrophage regulation and polarization via the HDAC1/miR-155 axis.

BACKGROUND: We recently found that butyrate could ameliorate inflammation of alcoholic liver disease (ALD) in mice. However, the exact mechanism remains incompletely comprehended. Here, we examined the role of butyrate on ALD-associated inflammation through macrophage (Mψ) regulation and polarization using in vivo and in vitro experiments. METHODS: For in vivo experiments, C57BL/6J mice were fed modified Lieber-DeCarli liquid diets supplemented with or without ethanol and sodium butyrate (NaB). After 6 weeks of treatment, mice were euthanized and associated indicators were analyzed. For in vitro experiments, lipopolysaccharide (LPS)-induced inflammatory murine RAW264.7 cells were treated with NaB or miR-155 inhibitor/mimic to verify the anti-inflammatory effect and underlying mechanism. RESULTS: The administration of NaB alleviated pathological damage and associated inflammation, including LPS, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß levels in ALD mice. NaB intervention restored the imbalance of macrophage polarization by inhibiting inducible nitric oxide synthase (iNOS) and elevating arginase-1 (Arg-1). Moreover, NaB reduced histone deacetylase-1 (HDAC1), nuclear factor kappa-B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and miR-155 expression in ALD mice, but also increased peroxisome proliferator-activated receptor-γ (PPAR-γ). Thus, MiR-155 was identified as a strong regulator of ALD. To further penetrate the role of miR-155, LPS-stimulated RAW264.7 cells co-cultured with NaB were treated with the specific inhibitor or mimic. Intriguingly, miR-155 was capable of negatively regulated inflammation with NaB intervention by targeting SOCS1, SHIP1, and IRAK-M genes. CONCLUSION: Butyrate suppresses the inflammation in mice with ALD by regulating macrophage polarization via the HDAC1/miR-155 axis, which may potentially contribute to the novel therapeutic treatment for the disease.

Impact of unilateral mastectomy on body posture: A prospective longitudinal observational study.

Objective: Unilateral mastectomy is known to induce postural alterations, yet the temporal development pattern of these changes remains elusive. This study aimed to explore the impact of unilateral mastectomy on body posture. Methods: A prospective, longitudinal, observational study with a one-group repeated-measures design was conducted. Patients undergoing unilateral mastectomy were recruited from a university-affiliated hospital in Western China and monitored for 12 months post-surgery. A trained nurse assessed seven postural baseline parameters on the day of suture removal and at 3, 6, and 12 months after unilateral mastectomy. Two parameters were in the sagittal plane (forward head posture and trunk rotation angle), and five were in the coronal plane (neck tilt, shoulder asymmetry, scapular asymmetry, scapular asymmetry relative to the spine, and pelvic tilt). Results: The final analysis included 159 patients. Baseline prevalence of most postural abnormalities ranged from 50.94% to 59.75%, with mean deviations between 2.74 and 4.51 mm. At 12 months post-mastectomy, prevalence and mean deviations increased by more than 30% and 3.50 mm, respectively, compared to baseline. Postural abnormalities increased gradually in the first 3 months, notably between the 3rd and 6th months, and slowed between the 6th and 12th months. On the mastectomy side, coronal plane abnormalities significantly increased within 12 months: earlobe to acromion distance (Wald χ2 = 45.283, P < 0.001), depressed shoulder height (Wald χ2 = 42.253, P < 0.001), depressed scapula height (Wald χ2 = 31.587, P < 0.001), scapula to spine distance (Wald χ2 = 45.283, P < 0.001), and elevated pelvic height (Wald χ2 = 48.924, P < 0.001). Conclusions: Postural changes are common post-unilateral mastectomy, with prevalence and deviation increasing gradually, particularly between 3 and 6 months post-mastectomy. Early rehabilitation initiation is recommended to mitigate postural changes. Trial registration: ChiCTR2000040897.

Drug development advances in human genetics-based targets.

Drug development is a long and costly process, with a high degree of uncertainty from the identification of a drug target to its market launch. Targeted drugs supported by human genetic evidence are expected to enter phase II/III clinical trials or be approved for marketing more quickly, speeding up the drug development process. Currently, genetic data and technologies such as genome-wide association studies (GWAS), whole-exome sequencing (WES), and whole-genome sequencing (WGS) have identified and validated many potential molecular targets associated with diseases. This review describes the structure, molecular biology, and drug development of human genetics-based validated beneficial loss-of-function (LOF) mutation targets (target mutations that reduce disease incidence) over the past decade. The feasibility of eight beneficial LOF mutation targets (PCSK9, ANGPTL3, ASGR1, HSD17B13, KHK, CIDEB, GPR75, and INHBE) as targets for drug discovery is mainly emphasized, and their research prospects and challenges are discussed. In conclusion, we expect that this review will inspire more researchers to use human genetics and genomics to support the discovery of novel therapeutic drugs and the direction of clinical development, which will contribute to the development of new drug discovery and drug repurposing.

Effects of the invasion of Ralstonia solanacearum on soil microbial community structure in Wuhan, China.

This study investigated the change in the microbiome of tomato rhizosphere soils after the invasion of Ralstonia solanacearum and analyzed the correlation between microbes and soil physicochemical properties. Diversity analyses of the bacteria in healthy and diseased rhizosphere soil samples (HRS and DRS) revealed that HRS had a higher species diversity and were compositionally different from DRS (P ≤ 0.05). Substantial differences in the relative abundance of Actinobacteria (37.52% vs 28.96%, P ≤ 0.05) and Proteobacteria (29.20% vs 35.59%, P ≤ 0.05) were identified in HRS and DRS, respectively. Taxonomic composition analysis showed ten differentially abundant genera, and seven of them (Gaiella, Roseisolibacter, Solirubrobacter, Kribbella, Acidibacter, Actinomarinicola, and Marmoricola) are more abundant in HRS. Soil pH and enzyme activities were negatively correlated with the abundance of R. solanacearum. The contents of total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkaline nitrogen (alkaline N), available phosphorus (AP), available potassium (AK), NO3-N(NN), NH4+-N (AN), and organic matter (OM) were all significantly increased in DRS. The composition and richness of protozoa in the samples show significant differences. Cephalobus, Acrobeles, Heteromita, norank_Tylenchida, and Rotylenchulus were enriched in DRS. Microbial interaction networks revealed that the HRS networks were more complex than the DRS networks. Overall, the results of this study demonstrate that healthy soil has a more complex microbial community structure and higher enzyme activity, and the invasion of R. solanacearum damages the soil microbial system.IMPORTANCEHow does the invasion of Ralstonia solanacearum affect tomato rhizosphere bacteria and protozoa? Which microbial changes can affect the growth of R. solanacearum? To date, most research studies focus on bacteria, with little research on protozoa, and even less on the synergistic effects between protozoa and bacteria. Here, we analyzed the correlation between tomato rhizosphere bacterial and protozoan communities and soil physicochemical properties during the invasion of R. solanacearum. We found that the diversity and abundance of rhizosphere microorganisms in healthy rhizosphere soil samples (HRS) were significantly higher than those in diseased rhizosphere soil samples (DRS), and there were significant changes in soil pH and enzyme activity. Overall, in this study, the analysis of microbial changes during the invasion of R. solanacearum provides a theoretical basis for the prevention and control of bacterial wilt.