Effect of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation on gastrointestinal reactions of malignant tumor patients undergoing chemotherapy. / éš”å§œç¸è”åˆæ¿é’ˆå¯¹æ¶æ€§è‚¿ç˜¤åŒ–ç–—æ‚£è€ èƒƒè‚ é“ååº”çš„å½±å“.

OBJECTIVES: To observe the efficacy and safety of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with malignant tumors. METHODS: Patients with malignant tumors and suffering from chemotherapy were randomly divided into control group (35 cases, 4 cases dropped off) and observation group (35 cases, 2 cases dropped off). The patients of the control group were treated by orally taking ondansetron hydrochloride tablets 8 mg/time, 3 times a day for 3 d, and those of the observation group treated by ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation of Zusanli(ST36), Neiguan(PC6), Tianshu(ST25), Zhongwan(CV12) and Guanyuan(CV4) once a day for a total of 3 d, based on the treatment of the control group. The patients' gastrointestinal reaction degree after the 1st , 2nd and the 3rd day of treatment were recorded. The Karnofsky performance status (KPS) score (0-100 points) was used for assessing the patients' quality of life. The TCM syndrome score (4 grades：no, mild, medium and severe, i.e. 0, 2, 4 and 6 points) was given according to the patients' severity of symptoms of spleen (stomach) qi deficiency (nausea and vomiting, abdominal distension after eating, belching, loss of appetite, weakness and laziness to speak, fatigue, and loose stool). The safety of the treatment was assessed by examining the patients' blood routine, liver function and kidney function, and the adverse reactions including blisters, allergies, burns and fainting during acupuncture treatment. RESULTS: After the 2nd and 3rd day of treatment, the patients conditions of vomiting and nausea in the observation group were significantly better than those of the control group (P<0.05). The TCM syndrome score and KPS score were significantly decreased in comparison with those of pre-treatment in both groups (P<0.05), and the TCM syndrome score was obviously lower in the observation group than in the control group (P<0.05). No significant differences were found between the two groups in the KPS score after the treatment , and in the levels of white blood cells (WBC), hemoglobin (HGB), platelets (PLT), absolute neutrophil count (ANC), alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine(Cr), and blood urea nitrogen (BUN). CONCLUSIONS: The use of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation is safe for CINV patients, and can effectively relieve nausea and vomiting and alleviate digestive symptoms.

FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Metabolic engineering of "last-line antibiotic" colistin in Paenibacillus polymyxa.

Colistin, also known as polymyxin E, is a lipopeptide antibiotic used to treat infections caused by multidrug-resistant gram-negative bacteria. It is considered a "last-line antibiotic", but its clinical development is hindered by low titer and impurities resulting from the presence of diverse homologs in microbial fermentation. To ensure consistent pharmaceutical activity and kinetics, it is crucial to have high-purity colistin active pharmaceutical ingredient (API) in the pharmaceutical industry. This study focused on the metabolic engineering of a natural colistin producer strain to produce colistin with a high titer and purity. Guided by genome mining, we identified Paenibacillus polymyxa ATCC 842 as a natural colistin producer capable of generating a high proportion of colistin A. By systematically inactivating seven non-essential biosynthetic gene clusters (BGCs) of peptide metabolites that might compete precursors with colistin or inhibit colistin production, we created an engineered strain, P14, which exhibited an 82% increase in colistin titer and effectively eliminated metabolite impurities such as tridecaptin, paenibacillin, and paenilan. Additionally, we engineered the L-2,4-diaminobutyric acid (L-2,4-DABA) pathway to further enhance colistin production, resulting in the engineered strain P19, which boosted a remarkable colistin titer of 649.3 mg/L - a 269% improvement compared to the original strain. By concurrently feeding L-isoleucine and L-leucine, we successfully produced high-purity colistin A, constituting 88% of the total colistin products. This study highlights the potential of metabolic engineering in improving the titer and purity of lipopeptide antibiotics in the non-model strain, making them more suitable for clinical use. These findings indicate that efficiently producing colistin API in high purity directly from fermentation can now be achieved in a straightforward manner.

The WDR11 complex is a receptor for acidic-cluster-containing cargo proteins.

Vesicle trafficking is a fundamental process that allows for the sorting and transport of specific proteins (i.e., "cargoes") to different compartments of eukaryotic cells. Cargo recognition primarily occurs through coats and the associated proteins at the donor membrane. However, it remains unclear whether cargoes can also be selected at other stages of vesicle trafficking to further enhance the fidelity of the process. The WDR11-FAM91A1 complex functions downstream of the clathrin-associated AP-1 complex to facilitate protein transport from endosomes to the TGN. Here, we report the cryo-EM structure of human WDR11-FAM91A1 complex. WDR11 directly and specifically recognizes a subset of acidic clusters, which we term super acidic clusters (SACs). WDR11 complex assembly and its binding to SAC-containing proteins are indispensable for the trafficking of SAC-containing proteins and proper neuronal development in zebrafish. Our studies thus uncover that cargo proteins could be recognized in a sequence-specific manner downstream of a protein coat.

Improving resistant starch content of cassava starch by pulsed electric field-assisted esterification.

This study aims to investigate the effect of pulsed electric field (PEF) assisted OSA esterification treatment on the multi-scale structure and digestive properties of cassava starch and structure-digestion relationships. The degree of substitution (DS) of starch dually modified at 1.5-4.5 kV/cm was 37.6-55.3 % higher than that of starch modified by the conventional method. Compared with native starch, the resistant starch (RS) content of esterified starch treated with 3 kV/cm significantly increased by 17.13 %, whereas that of starch produced by the conventional method increased by only 5.91 %. Furthermore, assisted esterification at low electric fields (1.5-3 kV/cm) promotes ester carbonyl grafting on the surface of starch granules, increases steric hindrance and promotes the rearrangement of the amorphous regions of starch, which increases the density of the double-helical structure. These structural changes slow down starch digestion and increase the RS content. Therefore, this study presents a potential method for increasing the RS content of starch products using PEF to achieve the desired digestibility.

Emergence of flat bands and ferromagnetic fluctuations via orbital-selective electron correlations in Mn-based kagome metal.

Kagome lattice has been actively studied for the possible realization of frustration-induced two-dimensional flat bands and a number of correlation-induced phases. Currently, the search for kagome systems with a nearly dispersionless flat band close to the Fermi level is ongoing. Here, by combining theoretical and experimental tools, we present Sc3Mn3Al7Si5 as a novel realization of correlation-induced almost-flat bands in the kagome lattice in the vicinity of the Fermi level. Our magnetic susceptibility, 27Al nuclear magnetic resonance, transport, and optical conductivity measurements provide signatures of a correlated metallic phase with tantalizing ferromagnetic instability. Our dynamical mean-field calculations suggest that such ferromagnetic instability observed originates from the formation of nearly flat dispersions close to the Fermi level, where electron correlations induce strong orbital-selective renormalization and manifestation of the kagome-frustrated bands. In addition, a significant negative magnetoresistance signal is observed, which can be attributed to the suppression of flat-band-induced ferromagnetic fluctuation, which further supports the formation of flat bands in this compound. These findings broaden a new prospect to harness correlated topological phases via multiorbital correlations in 3d-based kagome systems.

Wekemo Bioincloud: A user-friendly platform for meta-omics data analyses.

The increasing application of meta-omics approaches to investigate the structure, function, and intercellular interactions of microbial communities has led to a surge in available data. However, this abundance of human and environmental microbiome data has exposed new scalability challenges for existing bioinformatics tools. In response, we introduce Wekemo Bioincloud-a specialized platform for -omics studies. This platform offers a comprehensive analysis solution, specifically designed to alleviate the challenges of tool selection for users in the face of expanding data sets. As of now, Wekemo Bioincloud has been regularly equipped with 22 workflows and 65 visualization tools, establishing itself as a user-friendly and widely embraced platform for studying diverse data sets. Additionally, the platform enables the online modification of vector outputs, and the registration-independent personalized dashboard system ensures privacy and traceability. Wekemo Bioincloud is freely available at https://www.bioincloud.tech/.

The gut microbiota-aromatic hydrocarbon receptor (AhR) axis mediates the anticolitic effect of polyphenol-rich extracts from Sanghuangporus.

Inflammatory bowel disease (IBD) is a significant global health concern. The gut microbiota plays an essential role in the onset and development of IBD. Sanghuangporus (SH), a traditional Chinese medicinal mushroom, has excellent anti-inflammatory effects and is effective at modulating the gut microbiota. Despite these attributes, the specific anticolitic effects of SH and the mechanisms through which the gut microbiota mediates its benefits remain unclear. Herein, we demonstrated that polyphenol-rich extract from SH effectively alleviated the pathological symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by modulating the gut microbiota. Treatment with SH distinctly enriched Alistipes, especially Alistipes onderdonkii, and its metabolite 5-hydroxyindole-3-acetic acid (5HIAA). Oral gavage of live A. onderdonkii or 5HIAA potently mitigated DSS-induced colitis in mice. Moreover, both 5HIAA and SH significantly activated the aromatic hydrocarbon receptor (AhR), and the administration of an AhR antagonist abrogated their protective effects against colitis. These results underscore the potent efficacy of SH in diminishing DSS-induced colitis through the promotion of A. onderdonkii and 5HIAA, ultimately activating AhR signaling. This study unveils potential avenues for developing therapeutic strategies for colitis based on the interplay between SH and the gut microbiota.

ChatGPT and generative AI are revolutionizing the scientific community: A Janus-faced conundrum.

The advent of generative artificial intelligence (AI) technologies marks a transformative moment for the scientific sphere, unlocking novel avenues to elevate scientific writing's efficiency and quality, expedite insight discovery, and enhance code development processes. Essential to leveraging these advancements is prompt engineering, a method that enhances AI interaction efficiency and quality. Despite its benefits, effective application requires blending researchers' expertise with AI, avoiding overreliance. A balanced strategy of integrating AI with independent critical thinking ensures the advancement and quality of scientific research, leveraging innovation while maintaining research integrity.

Heterologous expression of the insect SVWC peptide WHIS1 inhibits Candida albicans invasion into A549 and HeLa epithelial cells.

Candida albicans (C. albicans), a microbe commonly isolated from Candida vaginitis patients with vaginal tract infections, transforms from yeast to hyphae and produces many toxins, adhesins, and invasins, as well as C. albicans biofilms resistant to antifungal antibiotic treatment. Effective agents against this pathogen are urgently needed. Antimicrobial peptides (AMPs) have been used to cure inflammation and infectious diseases. In this study, we isolated whole housefly larvae insect SVWC peptide 1 (WHIS1), a novel insect single von Willebrand factor C-domain protein (SVWC) peptide from whole housefly larvae. The expression pattern of WHIS1 showed a response to the stimulation of C. albicans. In contrast to other SVWC members, which function as antiviral peptides, interferon (IFN) analogs or pathogen recognition receptors (PRRs), which are the prokaryotically expressed MdWHIS1 protein, inhibit the growth of C. albicans. Eukaryotic heterologous expression of WHIS1 inhibited C. albicans invasion into A549 and HeLa cells. The heterologous expression of WHIS1 clearly inhibited hyphal formation both extracellularly and intracellularly. Furthermore, the mechanism of WHIS1 has demonstrated that it downregulates all key hyphal formation factors (ALS1, ALS3, ALS5, ECE1, HWP1, HGC1, EFG1, and ZAP1) both extracellularly and intracellularly. These data showed that heterologously expressed WHIS1 inhibits C. albicans invasion into epithelial cells by affecting hyphal formation and adhesion factor-related gene expression. These findings provide new potential drug candidates for treating C. albicans infection.

Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates.

Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.

Vaginal microbiota are associated with in vitro fertilization during female infertility.

The vaginal microbiome plays an essential role in the reproductive health of human females. As infertility increases worldwide, understanding the roles that the vaginal microbiome may have in infertility and in vitro fertilization (IVF) treatment outcomes is critical. To determine the vaginal microbiome composition of 1411 individuals (1255 undergoing embryo transplantation) and their associations with reproductive outcomes, clinical and biochemical features are measured, and vaginal samples are 16S rRNA sequenced. Our results suggest that both too high and too low abundance of Lactobacillus is not beneficial for pregnancy; a moderate abundance is more beneficial. A moderate abundance of Lactobacillus crispatus and Lactobacillus iners (~80%) (with a pregnancy rate of I-B: 54.35% and III-B: 57.73%) is found beneficial for pregnancy outcomes compared with a higher abundance (>90%) of Lactobacillus (I-A: 44.81% and III-A: 51.06%, respectively). The community state type (CST) IV-B (contains a high to moderate relative abundance of Gardnerella vaginalis) shows a similar pregnant ratio (48.09%) with I-A and III-A, and the pregnant women in this CST have a higher abundance of Lactobacillus species. Metagenome analysis of 71 samples shows that nonpregnant women are detected with more antibiotic-resistance genes, and Proteobacteria and Firmicutes are the main hosts. The inherent differences within and between women in different infertility groups suggest that vaginal microbes might be used to detect infertility and potentially improve IVF outcomes.

Visualizing set relationships: EVenn's comprehensive approach to Venn diagrams.

Venn diagrams serve as invaluable tools for visualizing set relationships due to their ease of interpretation. Widely applied across diverse disciplines such as metabolomics, genomics, transcriptomics, and proteomics, their utility is undeniable. However, the operational complexity has been compounded by the absence of standardized data formats and the need to switch between various platforms for generating different Venn diagrams. To address these challenges, we introduce the EVenn platform, a versatile tool offering a unified interface for efficient data exploration and visualization of diverse Venn diagrams. EVenn (http://www.ehbio.com/test/venn) streamlines the data upload process with a standardized format, enhancing the capabilities for multimodule analysis. This comprehensive protocol outlines various applications of EVenn, featuring representative results of multiple Venn diagrams, data uploads in the centralized data center, and step-by-step case demonstrations. Through these functionalities, EVenn emerges as a valuable and user-friendly tool for the in-depth exploration of multiomics data.

Sensory ASIC3 channel exacerbates psoriatic inflammation via a neurogenic pathway in female mice.

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.

Mannitol-coated hydroxypropyl methylcellulose as an alternative directly compressible controlled release excipient.

One of the most common forms of controlled release technology for oral drug delivery comprises an active ingredient dispersed in a hydrophilic matrix forming polymer such as hydroxypropyl methylcellulose (HPMC), which is tableted via direct compression. However, HPMC may pose problems in direct compression due to its poor flowability. Hence, mannitol syrup was spray-coated over fluidized HPMC particles to produce co-processed HPMC-mannitol at ratios of 20:80, 50:50, and 70:30. Particles of pure HPMC, co-processed HPMC-mannitol, and their respective physical mixtures were evaluated for powder flowability, compression profiles, and controlled release performance. It was found that co-processed HPMC-mannitol consisted of particles with improved flow compared to pure HPMC particles. Sufficiently strong tablets of >2 MPa could be produced at moderate to high compression forces of 150-200 MPa. The dissolution profile could be tuned to obtain desired release profiles by altering HPMC-mannitol ratios. Co-processed HPMC-mannitol offers an interesting addition to the formulator's toolbox in the design of controlled release formulations for direct compression.

Large-scale bacterial genomic and metagenomic analysis reveals Pseudomonas aeruginosa as potential ancestral source of tigecycline resistance gene cluster tmexCD-toprJ.

BACKGROUND: The global dissemination of the multidrug resistance efflux pump gene cluster tmexCD-toprJ has greatly weakened the effects of multiple antibiotics, including tigecycline. However, the potential origin and transmission mechanisms of the gene cluster remain unclear. METHODS: Here, we concluded a comprehensive bioinformatics analysis on integrated 73,498 bacterial genomes, including Pseudomonas spp., Klebsiella spp., Aeromonas spp., Proteus spp., and Citrobacter spp., along with 1,152 long-read metagenomic datasets to trace the origin and propagation of tmexCD-toprJ. RESULTS: Our results demonstrated that tmexCD-toprJ was predominantly found in Pseudomonas aeruginosa sourced from human hosts in Asian countries and North American countries. Phylogenetic and genomic feature analyses showed that tmexCD-toprJ was likely evolved from mexCD-oprJ of some special clones of P. aeruginosa. Furthermore, metagenomic analysis confirmed that P. aeruginosa is the only potential ancestral bacterium for tmexCD-toprJ. A putative mobile genetic structure harboring tmexCD-toprJ, int-int-hp-hp-tnfxB-tmexCD-toprJ, was the predominant genetic context of tmexCD-toprJ across various bacterial genera, suggesting that the two integrase genes play a pivotal role in the horizontal transmission of tmexCD-toprJ. CONCLUSIONS: Based on these findings, it is almost certain that the tmexCD-toprJ gene cluster was derived from P. aeruginosa and further spread to other bacteria.

Exploring the roles of ribosomal peptides in prokaryote-phage interactions through deep learning-enabled metagenome mining.

BACKGROUND: Microbial secondary metabolites play a crucial role in the intricate interactions within the natural environment. Among these metabolites, ribosomally synthesized and post-translationally modified peptides (RiPPs) are becoming a promising source of therapeutic agents due to their structural diversity and functional versatility. However, their biosynthetic capacity and ecological functions remain largely underexplored. RESULTS: Here, we aim to explore the biosynthetic profile of RiPPs and their potential roles in the interactions between microbes and viruses in the ocean, which encompasses a vast diversity of unique biomes that are rich in interactions and remains chemically underexplored. We first developed TrRiPP to identify RiPPs from ocean metagenomes, a deep learning method that detects RiPP precursors in a hallmark gene-independent manner to overcome the limitations of classic methods in processing highly fragmented metagenomic data. Applying this method to metagenomes from the global ocean microbiome, we uncover a diverse array of previously uncharacterized putative RiPP families with great novelty and diversity. Through correlation analysis based on metatranscriptomic data, we observed a high prevalence of antiphage defense-related and phage-related protein families that were co-expressed with RiPP families. Based on this putative association between RiPPs and phage infection, we constructed an Ocean Virus Database (OVD) and established a RiPP-involving host-phage interaction network through host prediction and co-expression analysis, revealing complex connectivities linking RiPP-encoding prokaryotes, RiPP families, viral protein families, and phages. These findings highlight the potential of RiPP families involved in prokaryote-phage interactions and coevolution, providing insights into their ecological functions in the ocean microbiome. CONCLUSIONS: This study provides a systematic investigation of the biosynthetic potential of RiPPs from the ocean microbiome at a global scale, shedding light on the essential insights into the ecological functions of RiPPs in prokaryote-phage interactions through the integration of deep learning approaches, metatranscriptomic data, and host-phage connectivity. This study serves as a valuable example of exploring the ecological functions of bacterial secondary metabolites, particularly their associations with unexplored microbial interactions. Video Abstract.

Deciphering the Enigma of Intramyocardial Hemorrhage Following Reperfusion Therapy in Acute ST-Segment Elevation Myocardial Infarction: A Comprehensive Exploration from Mechanisms to Therapeutic Strategies.

Acute ST-segment elevation myocardial infarction (STEMI) is a formidable challenge in cardiovascular medicine, demanding advanced reperfusion strategies such as emergency percutaneous coronary intervention. While successful revascularization is pivotal, the persistent "no-reflow" phenomenon remains a clinical hurdle, often intertwined with microvascular dysfunction. Within this intricate scenario, the emergence of intramyocardial hemorrhage (IMH) has garnered attention as a significant contributor. This review offers a detailed exploration of the multifaceted relationship between IMH and the "no-reflow" phenomenon, delving into the mechanisms governing IMH occurrence, state-of-the-art diagnostic modalities, predictive factors, clinical implications, and the evolving landscape of preventive and therapeutic strategies. The nuanced examination aims to deepen our comprehension of IMH, providing a foundation for the identification of innovative therapeutic avenues and enhanced clinical outcomes for STEMI patients.