Influence of Salvia miltiorrhizae on the Mesenteric Lymph Node of Rats with Severe Acute Pancreatitis or Obstructive Jaundice

Objective. To observe the effect of salvia miltiorrhizae injection on inflammatory mediator levels and mesenteric lymph nodes in severe acute pancreatitis (SAP) and obstructive jaundice (OJ) rats and explore the protective mechanism of salvia miltiorrhizae on the lymph nodes of these rats. Methods. A total of 288 rats were used in SAP-associated and OJ-associated experiments. The rats were randomly divided into sham-operated group, model control group, and treated group. At various time points after operation, the pathological changes in mesenteric lymph nodes of rats in each group were observed, respectively. Results. The pathological severity scores in lymph nodes of SAP rats in treated group were significantly lower than those in model control group (P < .05) while the pathological changes in lymph nodes of OJ rats in treated group also showed varying degrees of mitigation. Conclusion. Salvia miltiorrhizae can exert protective effects on the lymph nodes of SAP or OJ rats via a mechanism that is associated with reducing the contents of inflammatory mediators in blood

Establishment and Development of Oral Microflora in 12–24 Month-Old Toddlers Monitored by High-Throughput Sequencing

A cohort study was conducted to evaluate oral microbial diversity among toddlers aged 12–24 months, and to describe the dynamic processes of colonization, development, and stabilization of the oral microflora during tooth eruption using high-throughput sequencing technology. A total of 20 healthy toddlers aged 12 months were included at baseline and followed up through 18–24 months. Clinical oral examinations of dental caries status and visible plaque index were carried out at three follow-up time points. Pooled supragingival plaque biofilm samples were also collected at ages 12, 18, and 24 months. Plaque biofilm DNA was extracted and analyzed by MiSeq sequencing. A total of 18 toddlers completed three follow-ups. At 12 months of age, all the toddlers only had eruption of the anterior teeth, without dental caries. At ages 18 and 24 months, one and two toddlers showed two and three teeth with carious white spots, respectively. Depth, Good's coverage, and sample size of sequencing were reasonable. The dominant bacterial genera in the oral cavity of 12-month-old toddlers were Capnocytophaga, Neisseria, Streptococcus, Kingella, and Leptotrichia; the oral microflora composition was relatively stable by 18 months of age and included unclassified Enterobacteriaceae, Selenomonas, Prevotella, Leptotrichia, and Veillonella as the dominant genera; unclassified Enterobacteriaceae, Streptococcus, Neisseria, Leptotrichia, and Selenomonas were the dominant genera by 24 months. There were significant differences among microbial compositions in the oral cavities of 12, 18, and 24-month-old toddlers, with relatively small differences observed between the 18 and 24 months samples. In conclusion, oral microbial community of toddlers showed a trend of dynamic development. Significant differences in oral microbial diversity among toddlers aged 12–24 months were observed, while the microbial diversity differences among toddlers aged 18–24 months tended to be more similar. The findings indicated that the oral microbial community gradually matures and tends to stabilize with the growth and development of toddlers

Biological cohesion as the architect of bed movement under wave action

Funding for this project was provided by the National Key Research and Development Project, MOST, China (2018YFC0407506), the National Natural Science Foundation of China (51620105005), and the China Postdoctoral Science Foundation (2020M680580). D. M. Paterson acknowledges NERC funding (NE/N016009/1).Cohesive extracellular polymeric substances (EPS) generated by microorganisms abundant on Earth are regarded as bed “stabilizers” increasing the erosion threshold in sedimentary systems. However, most observations of this phenomenon have been taken under steady flow conditions. In contrast, we present how EPS affect the bed movement under wave action, showing a destabilization of the system. We demonstrate a complex behavior of the bio‐sedimentary deposits, which encompasses liquefaction, mass motion, varying bed formations and erosion, depending on the amount of EPS present. Small quantities of EPS induce higher mobility of the sediments, liquefying an otherwise stable bed. Bed with larger quantities of EPS undergoes a synchronized mechanical oscillation. Our analysis clarifies how biological cohesion can potentially put coastal wetlands at risk by increasing their vulnerability to waves. These findings lead to a revised understanding of the different roles played by microbial life, and their importance as mediators of seabed mobility.Publisher PDFPeer reviewe

CLHA: A Simple yet Effective Contrastive Learning Framework for Human Alignment

Reinforcement learning from human feedback (RLHF) is a crucial technique in aligning large language models (LLMs) with human preferences, ensuring these LLMs behave in beneficial and comprehensible ways to users. However, a longstanding challenge in human alignment techniques based on reinforcement learning lies in their inherent complexity and difficulty in training. To address this challenge, we present a simple yet effective Contrastive Learning Framework for Human Alignment (CLHA) to align LLMs with human preferences directly. CLHA employs a novel rescoring strategy to evaluate the noise within the data by considering its inherent quality and dynamically adjusting the training process. Simultaneously, CLHA utilizes pairwise contrastive loss and adaptive supervised fine-tuning loss to adaptively modify the likelihood of generating responses, ensuring enhanced alignment with human preferences. Using advanced methods, CLHA surpasses other algorithms, showcasing superior performance in terms of reward model scores, automatic evaluations, and human assessments on the widely used ``Helpful and Harmless'' dataset

Potential adverse events associated with sphingosine-1-phosphate (S1P) receptor modulators in patients with multiple sclerosis: an analysis of the FDA adverse event reporting system (FAERS) database

ObjectiveSphingosine-1-phosphate receptor (S1PR) modulators have recently attracted increasing attention for the treatment of multiple sclerosis (MS). Despite their preference in the clinic, multiple adverse events (AEs) continue to be reported every year. This study aimed to investigate the potential AEs as well as related important medical events (IMEs) signal associated with S1PR modulators, including fingolimod, siponimod and ozanimod in a real-world study using the FDA Adverse Event Reporting System (FAERS) database.MethodsAll data were collected from the FAERS database, spanning from the fourth quarter of 2010(2010Q4) to the second quarter of 2023 (2023Q2). Potential AE and IME signals of S1PR modulators were identified based on a disproportionality analysis using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and the bayesian confidence propagation neural network of information components (IC).ResultsOverall, 276,436 reports of fingolimod, 20,972 reports of siponimod and 10,742 reports of ozanimod were analyzed from the FAERS database. Among reports, females were more prone to develop AEs (73.71% for females vs. 23.21% for males), and more than 50% of patients suffered from AEs were between 18 and 64 years. Subsequently, we investigated the top 20 AEs associated with the signal strength of S1PR modulators at the preferred term (PT) level, and identified 31 (8 vs. 11 vs. 12, respectively) unlabeled risk signals such as thrombosis, uterine disorder and reproductive system and breast disorders. Furthermore, we discovered that the S1PR modulator reported variations in the possible IMEs, and that the IMEs associated with ocular events were reported frequently. It’s interesting to note that infection and malignancy are prominent signals with both fingolimod and siponimod in the top 20 PTs related to mortality reports.ConclusionThe present investigation highlights the possible safety risks associated with S1PR modulators. The majority of AEs are generally consistent with previous studies and are mentioned in the prescribing instructions, however, several unexpected AE signals have also been observed. Ozanimod showed the lowest signal intensity and a better safety profile than the other S1PR modulators. Due to the short marketing time of drugs and the limitations of spontaneous reporting database, further research is required to identify potential AEs related to S1PR modulators

Progress of nanoparticle drug delivery system for the treatment of glioma

Gliomas are typical malignant brain tumours affecting a wide population worldwide. Operation, as the common treatment for gliomas, is always accompanied by postoperative drug chemotherapy, but cannot cure patients. The main challenges are chemotherapeutic drugs have low blood-brain barrier passage rate and a lot of serious adverse effects, meanwhile, they have difficulty targeting glioma issues. Nowadays, the emergence of nanoparticles (NPs) drug delivery systems (NDDS) has provided a new promising approach for the treatment of gliomas owing to their excellent biodegradability, high stability, good biocompatibility, low toxicity, and minimal adverse effects. Herein, we reviewed the types and delivery mechanisms of NPs currently used in gliomas, including passive and active brain targeting drug delivery. In particular, we primarily focused on various hopeful types of NPs (such as liposome, chitosan, ferritin, graphene oxide, silica nanoparticle, nanogel, neutrophil, and adeno-associated virus), and discussed their advantages, disadvantages, and progress in preclinical trials. Moreover, we outlined the clinical trials of NPs applied in gliomas. According to this review, we provide an outlook of the prospects of NDDS for treating gliomas and summarise some methods that can enhance the targeting specificity and safety of NPs, like surface modification and conjugating ligands and peptides. Although there are still some limitations of these NPs, NDDS will offer the potential for curing glioma patients