Lipidomics revealed alterations in glycerophospholipid metabolism in skin squamous cell carcinoma.

Background: Skin squamous cell carcinoma (SCC) is a prevalent malignancy, and dysregulated lipid metabolism has been implicated in its pathogenesis. However, detailed characterization of lipid alterations in SCC remains limited. Methods: We analyzed lipid metabolic variations in tissue samples from 34 SCC patients and adjacent healthy tissues (located more than 1 cm from the tumor margin) using liquid chromatography-mass spectrometry (LC-MS). Data visualization and discriminatory lipid profiles were identified using principal component analysis (PCA) and sparse partial least squares discriminant analysis (sPLS-DA). Key lipids involved in the SCC metabolism were identified and further validated using an external data set (from a previous study, which similarly explored lipid profiles in oral SCC using lipidomics approaches). Pathway enrichment analysis was conducted to elucidate the metabolic pathways associated with these key lipids. Results: Eight lipids were identified by comparing SCC and healthy tissues including PI(16:0/22:4), PI(18:1/20:4), PE(16:0/20:4), PE(16:0/22:5), PE(16:0/22:6), PE(18:1/20:3), PC(18:1/20:2), and PC(18:2/20:2), as confirmed by independent datasets. All of these lipids were upregulated in SCC tumor tissues. Pathway enrichment analysis revealed significant alterations in glycerophospholipid metabolic pathways, particularly affecting the metabolism of diacylglycerophosphocholines, glycerophosphoethanolamines, and glycerophosphoinositols. Conclusion: Our findings reveal that dysregulated glycerophospholipid metabolism plays a pivotal role in the development of SCC.

First Report of Powdery mildew caused by Golovinomyces ambrosiae on Bidens pilosa in Guangdong Province, China.

Bidens pilosa L., an annual herbaceous plant with a wide distribution, possesses novel medicinal properties. In January 2021, a powdery mildew disease outbreak was documented on B. pilosa plants located in the roadside areas in Shenzhen, Guangdong Province, China, with 60 to 80% disease incidence. Initial symptoms manifested as small, irregular white powdery patches, primarily on the adaxial surfaces of leaves. Subsequently, the colonies expanded, forming coalescent colonies that spread across the leaves, petioles, and stems, eventually leading to the distortion and senescence of leaves. Hyphae are hyaline, flexuous to straight, septate, with thin walls and a width ranging from 2 to 8 µm. Hyphal appressoria are nipple-shaped. Conidophores are erect or slightly flexuous, ranging from 80 to 150 µm in length and 12 to 18 µm in width (n = 30). Typically, these conidophores bear chains of 2 to 5 immature conidia, displaying a sinuate outline. Foot-cells, located at the base of conidophores, are cylindrical and erect, approximately 33 to 100 µm in length and 6 to 10 µm in width (n = 30). Conidia are hyaline, ellipsoid-ovoid to barrel-shaped, and lack fibrosin bodies. Primary conidia are ellipsoid-ovoid in shape, characterized by a rounded apex and a subtruncate base, 25 to 40 µm × 15 to 22 µm in width. Secondary conidia are barrel-shaped with truncate or subtruncate ends, 27 to 35 µm × 15 to 20 µm in width. Germ tubes exhibit a longitubus pattern and are prominently produced at the perihilar or apical region of the conidia. No chasmothecia were observed in the collected samples. In order to conduct a molecular-level identification, mycelium and conidia were collected from B. pilosa leaves. Genomic DNA was subsequently extracted from these samples. The internal transcribed spacer (ITS), intergenic spacer (IGS) and beta-tubulin (tub2) sequences were performed using primer pairs ITS1/ITS4, IGS-12a/NS1R, and tub2, respectively (Carbone and Kohn 1999; Scholin et al. 1994; White et al.,1990). A 568-bp ITS, a 366-bp IGS, and a 354-bp tub2 sequences (GenBank accession nos. OR647592, OR978282 and OR978283) were obtained. The ITS sequence exhibited over 99.6% similarity to Golovinomyces ambrosiae (MT929773) and G. cichoracearum (MH590731). The IGS sequence displayed 100% similarity to G. ambrosiae (MK383490) and G. ambrosiae (OK349420). The tub2 sequence displayed 100% similarity to G. ambrosiae (MW981257) and G. ambrosiae (MW981256). Phylogenetic analysis of IGS, ITS and tub2 also grouped obtained sequences within the G. ambrosiae complex. Based on the analysis of morphological characteristics and sequence identity, the pathogen was identified as G. ambrosiae. In order to satisfy Koch's postulates, an infected leaf was carefully pressed onto leaves of six healthy young B. pilosa plants, each grown in a separate pot. Additionally, a control group consisted of six non-inoculated plants. All plants were placed in a greenhouse: 25°C, 14/10-h light/dark photoperiod, and relative humidity 50%. After 10 days, the inoculated leaves exhibited powdery mildew colonies similar to those observed in the original infected plants. At 16 days, the inoculated leaves exhibited discoloration and premature leaf drop. The pathogenicity test was conducted twice. Microscopic observation and sequencing confirmed that isolated fungus was identical to the original pathogen. G. ambrosiae has previously been documented on B. pilosa in Fuzhou, Fujian Province, China (Mukhtar et al., 2022). However, to the best of our knowledge, this study represents the first report of powdery mildew caused by G. ambrosiae on B. pilosa in Shenzhen, Guangdong Province, China.

Crystallization of smooth amorphous calcium phosphate microspheres to core-shell hydroxyapatite microspheres.

Calcium phosphates (Ca-P) represent a significant class of biological minerals found in natural hard tissues. Crystallization through phase transformation of a metastable precursor is an effective strategy to guide the growth of crystalline Ca-P with exceptional functionality. Despite extensive research on Ca-P, the exact process during the crystallization of amorphous particles to hydroxyapatite (HA) remains elusive. Herein, pure HA microspheres with a core-shell structure are crystallized via dissolution and re-crystallization of smooth amorphous calcium phosphate (ACP) microspheres. The transformation is initiated with the increase of the hydrothermal treatment time in the presence of sodium trimetaphosphate and l-glutamic. The underlying mechanisms along with the kinetics of such transformation are explored. Nanocrystalline areas are formed on the smooth ACP microspheres and crystallization advances via nanometre-sized clusters formed by directional arrangement of nanocrystalline whiskers. Our findings shed light on a crucial but unclear stage in the genesis of HA crystals, specifically under the conditions of hydrothermal synthesis.

Initial solution pH value for the construction of a 3D hydroxyapatite via the trisodium citrate-assisted hydrothermal route.

In this study, a trisodium citrate (TSC)-assisted hydrothermal method is utilized to prepare three-dimensional hydroxyapatite (3D HA). Understanding the role of TSC in the preparation of 3D HA crystals may provide valuable methods to design advanced biomaterials. As one of the indexes of solution supersaturation, the initial pH (ipH) value can not only directly affect the nucleation rate, but also affect the growth of HA crystals. In this work, the effect of the ipH on the microstructure, particle size distribution, and specific surface area of the 3D HA is explored. Results showed that the morphology of 3D HA transformed from a bundle to a dumbbell ball and then a dumbbell with an increase in the ipH. A corresponding mechanism of such a structural evolution was proposed, providing inspiration for the fabrication of innovative 3D HA structures with enhanced biological functionality and performance.

Association between single and multiple cardiometabolic diseases and all-cause mortality among Chinese older adults: A prospective, nationwide cohort study.

BACKGROUND AND AIM: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population. METHODS AND RESULTS: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001). CONCLUSIONS: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs.

Integration of Gut Microbiota, Serum Metabolomic, and Network Pharmacology to Reveal the Anti Insomnia Mechanism of Mongolian Medicine Sugemule-4 Decoction on Insomnia Model Rats.

Objective: To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating insomnia. Methods: DL-4-chlorophenylalanine (PCPA) + chronic unpredictable mild stress stimulation (CUMS) was used to induce an insomnia model in rats. After the model was successfully established, MMS-4D was intervened at low, medium, and high doses for 7 days. The open-field test (OFT) was used to preliminarily evaluate the efficacy. The potential mechanism of MMS-4D in treating insomnia was investigated using gut microbiota, serum metabolomics, and network pharmacology (NP). Experimental validation of the main components of the key pathways was carried out using ELISA and Western blot. Results: The weights of the insomnia-model rats were significantly raised (p ≤ 0.05), the total exercise distance in the OFT increased (p ≤ 0.05), the rest time shortened, and the number of standing times increased (p ≤ 0.05), after treatment with MMS-4D. Moreover, there was a substantial recovery in the 5-HT, DA, GABA, and Glu levels in the hypothalamus tissue and the 5-HT and GABA levels in the colon tissue of rats. The expression of DAT and DRD1 proteins in the hippocampus of insomnia rats reduced after drug treatment. MMS-4D may treat insomnia by regulating different crucial pathways including 5-HT -, DA -, GABA -, and Glu-mediated neuroactive light receiver interaction, cAMP signaling pathway, serotonergic, glutamatergic, dopaminergic, and GABAergic synapses. Conclusion: This study revealed that MMS-4D can improve the general state and behavioral changes of insomnia model rats. Its mechanism may be related to the reversal of abnormal pathways mediated by 5-HT, DA, GABA, and Glu, such as Serotonergic synapse, Dopaminergic synapse, Glutamatergic synapse, and GABAergic synapse.

Adoptive transfer of personalized neoantigen-reactive TCR-transduced T cells in metastatic colorectal cancer: phase 2 trial interim results.

Adoptive cell transfer (ACT) with neoantigen-reactive T lymphocytes can mediate cancer regression. Here we isolated unique, personalized, neoantigen-reactive T cell receptors (TCRs) from tumor-infiltrating lymphocytes of patients with metastatic gastrointestinal cancers and incorporated the TCR α and ß chains into gamma retroviral vectors. We transduced autologous peripheral blood lymphocytes and adoptively transferred these cells into patients after lymphodepleting chemotherapy. In a phase 2 single-arm study, we treated seven patients with metastatic, mismatch repair-proficient colorectal cancers who had progressive disease following multiple previous therapies. The primary end point of the study was the objective response rate as measured using RECIST 1.1, and the secondary end points were safety and tolerability. There was no prespecified interim analysis defined in this study. Three patients had objective clinical responses by RECIST criteria including regressions of metastases to the liver, lungs and lymph nodes lasting 4 to 7 months. All patients received T cell populations containing ≥50% TCR-transduced cells, and all T cell populations were polyfunctional in that they secreted IFNγ, GM-CSF, IL-2 and granzyme B specifically in response to mutant peptides compared with wild-type counterparts. TCR-transduced cells were detected in the peripheral blood of five patients, including the three responders, at levels ≥10% of CD3+ cells 1 month post-ACT. In one patient who responded to therapy, ~20% of CD3+ peripheral blood lymphocytes expressed transduced TCRs more than 2 years after treatment. This study provides early results suggesting that ACT with T cells genetically modified to express personalized neoantigen-reactive TCRs can be tolerated and can mediate tumor regression in patients with metastatic colorectal cancers. ClinicalTrials.gov registration: NCT03412877 .

Mycobacterium vaccae attenuates airway inflammation by inhibiting autophagy and activating PI3K/Akt signaling pathway in OVA-induced allergic airway inflammation mouse model.

PURPOSE: The etiology of asthma remains elusive, with no known cure. Based on accumulating evidence, autophagy, a self-degradation process that maintains cellular metabolism and homeostasis, participates in the development of asthma. Mycobacterium vaccae vaccine (M. vaccae), an immunomodulatory agent, has previously been shown to effectively alleviate airway inflammation and airway remodeling. However, its therapeutic effect on asthma via the regulation of autophagy remains unknown. Therefore, this study aimed to investigate the impact of M. vaccae in attenuating asthma airway inflammation via autophagy-mediated pathways. METHODS: Balb/c mice were used to generate an ovalbumin (OVA)-immunized allergic airway model and were subsequently administered either M. vaccae or M. vaccae + rapamycin (an autophagy activator) prior to each challenge. Next, airway inflammation, mucus secretion, and airway remodeling in mouse lung tissue were assessed via histological analyses. Lastly, the expression level of autophagy proteins LC3B, Beclin1, p62, and autolysosome was determined both in vivo and in vitro, along with the expression level of p-PI3K, PI3K, p-Akt, and Akt in mouse lung tissue. RESULTS: The findings indicated that aerosol inhalation of M. vaccae in an asthma mouse model has the potential to decrease eosinophil counts, alleviate airway inflammation, mucus secretion, and airway remodeling through the inhibition of autophagy. Likewise, M. vaccae could reduce the levels of OVA-specific lgE, IL-5, IL-13, and TNF-α in asthma mouse models by inhibiting autophagy. Furthermore, this study revealed that M. vaccae also suppressed autophagy in IL-13-stimulated BEAS-2B cells. Moreover, M. vaccae may activate the PI3K/Akt signaling pathway in the lung tissue of asthmatic mice. CONCLUSION: In summary, the present study suggests that M. vaccae may contribute to alleviating airway inflammation and remodeling in allergic asthma by potentially modulating autophagy and the PI3K/Akt signaling pathway. These discoveries offer a promising avenue for the development of therapeutic interventions targeting allergic airway inflammation.

Mitochondrial inorganic polyphosphate is required to maintain proteostasis within the organelle.

The existing literature points towards the presence of robust mitochondrial mechanisms aimed at mitigating protein dyshomeostasis within the organelle. However, the precise molecular composition of these mechanisms remains unclear. Our data show that inorganic polyphosphate (polyP), a polymer well-conserved throughout evolution, is a component of these mechanisms. In mammals, mitochondria exhibit a significant abundance of polyP, and both our research and that of others have already highlighted its potent regulatory effect on bioenergetics. Given the intimate connection between energy metabolism and protein homeostasis, the involvement of polyP in proteostasis has also been demonstrated in several organisms. For example, polyP is a bacterial primordial chaperone, and its role in amyloidogenesis has already been established. Here, using mammalian models, our study reveals that the depletion of mitochondrial polyP leads to increased protein aggregation within the organelle, following stress exposure. Furthermore, mitochondrial polyP is able to bind to proteins, and these proteins differ under control and stress conditions. The depletion of mitochondrial polyP significantly affects the proteome under both control and stress conditions, while also exerting regulatory control over gene expression. Our findings suggest that mitochondrial polyP is a previously unrecognized, and potent component of mitochondrial proteostasis.

Study on hormone induction of the male parent and embryonic development, gonad differentiation, and growth of "All-female No.1" Culter alburnus.

Female Culter alburnus was faster in growth rate than males. In this study, the gynogenetic G2 and the pseudo-male G2' were used as the female and male parents, respectively, to breed a new national variety "All-female No.1" C. alburnus (AFC). Hormone induction, embryonic development, gonadal differentiation, and growth of AFC were studied. The results showed induction with low concentrations of 17α-methyltestosterone in a indoor-net cage culture was not effective. Under the stimulation of 17α-methyltestosterone, some gonads had a tendency to transform into testis, but not completely. There were three types of gonads in 5-month-old and four types of gonads in 12-month-old fishes, however, they all differentiated into ovaries in 15-month-old fishes. Testosterone propionate and high concentrations of 17α-methyltestosterone in pond culture induction had a good effect resulting in ①a functional pseudo-male with normal testis development that could successfully extrude semen during the breeding period, ②a pseudo-male with normal testis development, but could not extrude semen, and ③the appearance of intersexual glands. The second experiment revealed that with common fish, all-female fish embryo had normal embryonic development. The development time and morphological characteristics of each stage were similar, but the development of the all-female embryo was slightly slower than the common embryos. The gonad differentiation of the all-female embryo were normal and none differentiated into testis, which indicated that all-female could ensure the female sex without affecting the normal gonad differentiation. The correlation between body weight, length, and month-age of all-female and common fish was strong. The all-female had faster growth rate and more uniform growth specification than the common fish. Therefore, the use of testosterone propionate and high concentrations of 17α-methyltestosterone in pond culture induction could avoid complete degeneration of gonads into ovaries. The all-female embryo had the advantages of normal embryonic development and gonadal differentiation, faster growth, and uniform growth specification.

Association between tobacco smoke exposure and serum parathyroid hormone levels among US adults (NHANES 2003-2006).

Tobacco smoke exposure has been demonstrated to impede bone remodeling and diminish bone density, yet research regarding its correlation with parathyroid hormone (PTH) remains limited. This study aims to investigate the relationship between tobacco smoke exposure and serum PTH levels in adults aged 20 years and older. This study included 7,641 participants from two cycles of the National Health and Nutrition Examination Survey (NHANES, United States, 2003- 2006). Reflect tobacco smoke exposure through serum cotinine levels, and use an adjusted weighted multivariate linear regression model to test the independent linear relationship between serum cotinine and PTH. Stratified analysis was conducted to validate the sensitivity of the conclusions. Smooth curve fitting and threshold effect analysis were performed to assess the non-linear relationship. After comprehensive adjustment using weighted multivariate regression analysis, a negative correlation was found between serum cotinine and PTH levels. The interaction p-values in subgroup analyses were all greater than 0.05. Moreover, smooth curve fitting indicated a non-linear relationship between serum cotinine and PTH, with a turning point observed. Our research indicates that tobacco smoke exposure is negatively correlated and independent of serum parathyroid hormone levels, indicating that long-term tobacco smoke exposure may lead to parathyroid dysfunction in adults.

[Effect of metabolic reprogramming on abdominal aortic aneurysm].

Abdominal aortic aneurysm (AAA) is a life-threatening disease that remains undetected until it acutely ruptures. Due to lack of effective pharmaceutic therapies, it is urgent to explore new prevention and treatment strategies. Metabolic reprogramming is a cellular process through which cells change their metabolic patterns to meet material and energy requirements, including glucose metabolism, lipid metabolism and amino acid metabolism. Recently, the regulatory role of metabolic reprogramming in cardiovascular diseases, especially AAA, has attracted significant attention. This review article focuses on the research progress regarding the effects of metabolic reprogramming of vascular smooth muscle cells (VSMCs) and macrophages on the occurrence and development of AAA, especially their roles in major pathological processes such as VSMCs apoptosis and phenotype transformation, extracellular matrix remodeling, oxidative stress, and inflammatory response. The aim is to provide new clues for the mechanism research and clinical treatment of AAA from the perspective of metabolism.

Antifungal bioactivity of Sarcococca hookeriana var. digyna Franch. against fluconazole-resistant Candida albicans in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Sarcococca hookeriana var. digyna Franch. has been widely utilized in folk medicine by the Miao people in the southwestern region of China for treating skin sores which may be associated with microbial infection. AIM OF THE STUDY: To investigate the antifungal bioactivity of S. hookeriana var. digyna against fluconazole-resistant Candida albicans in vitro and in vivo, as well as its underlying mechanism and the key bioactive component. MATERIALS AND METHODS: The antifungal bioactivity of 80% ethanol extract of S. hookeriana var. digyna (SHE80) was investigated in vitro using the broth microdilution method, time-growth curve, and time-kill assay. Its key functional component and antifungal mechanism were explored with combined approaches including UPLC-Q-TOF-MS, network pharmacology and metabolomics. The antifungal pathway was further supported via microscopic observation of fungal cell morphology and examination of its effects on fungal biofilm and cell membranes using fluorescent staining reagents. In vivo assessment of antifungal bioactivity was conducted using a mouse model infected with C. albicans on the skin. RESULTS: S. hookeriana var. digyna suppressed fluconazole-resistant C. albicans efficiently (MIC = 16 µg/mL, MFC = 64 µg/mL). It removed fungal biofilm, increased cell membrane permeability, induced protein leakage, reduced membrane fluidity, disrupted mitochondrial membrane potential, induced the release of reactive oxygen species, promoted cell apoptosis, and inhibited the transformation of fungi from the yeast state to the hyphal state significantly. In terms of mechanism, it affected sphingolipid metabolism and signaling pathway. Moreover, the predicted bioactive component, sarcovagine D, was supported by antifungal bioactivity evaluation in vitro (MIC = 4 µg/mL, MFC = 16 µg/mL). Furthermore, S. hookeriana var. digyna promoted wound healing, reduced the number of colony-forming units, and reduced inflammation effectively in vivo. CONCLUSIONS: The traditional use of S. hookeriana var. digyna for fungal skin infections was supported by antifungal bioactivity investigated in vitro and in vivo. Its mechanism and bioactive component were predicted and confirmed by experiments, which also provided a new antifungal agent for future research.

Effect of proton pump inhibitors versus histamine-2 receptor antagonists on acute kidney injury in septic patients at high risk for developing stress ulcers.

BACKGROUND: To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. METHODS: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. RESULTS: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). CONCLUSIONS: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.

Antibody-secreting cells as a source of NR1-IgGs in N-methyl-D-aspartate receptor-antibody encephalitis.

BACKGROUND: The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is known, but the immunobiological mechanisms underlying their production remain unclear. METHODS: For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum NR1-IgGs levels. Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro. RESULTS: For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pre-germinal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs. CONCLUSIONS: These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis.

Metagenomic analysis revealed the association between gut microbiota and different ovary responses to controlled ovarian stimulation.

The aim of this study was to assess the correlation between gut microbial taxonomy and various ovarian responses to controlled ovarian stimulation. A total of 22 IVF cycles with a follicle-to-oocyte index (FOI) < 0.5 and 25 IVF cycles with FOI ≥ 0.5 were included in this study. Baseline demographic characteristics were compared between the two groups. Metagenomic sequencing was performed to analyze fecal microbial community profiles. Mice were used to evaluate the effect of Bifidobacterium_longum on ovarian response to stimulation. Compared with FOI < 0.5 group, women in group with FOI ≥ 0.5 had significant more oocytes retrieved (p < 0.01). Prevotella_copri, Bateroides_vulgatus, Escherichia_coli and Bateroides_stercoris were more abundant in FOI < 0.5 group while Bifidobacterium_longum, Faecalibacterium_prausnitzii, Ruminococcus_gnavus and Bifidobacterium_pseudocatenula were more abundant in FOI ≥ 0.5 group. After adjusting for women's age and BMI, Pearson correlation analysis indicated alteration of gut microbiome was related with serum E2, FSH, number of oocytes retrieved and clinical pregnancy rate. Animal study showed ovarian response will be improved after Bifidobacterium_longum applied. An increased abundance of Bacteroidetes and Prevotella copri, as well as a decreased abundance of Bifidobacterium longum, have been found to be associated with poor ovarian responsiveness. Changes in gut microbiomes have been observed to be correlated with certain clinical characteristics. The potential enhancement of ovarian response may be facilitated by the integration of Bifidobacterium longum.

Self-shedding MOF-nanocarriers modulated CdS/MoSe2 heterojunction activity through in-situ ion exchange: An enhanced split-type photoelectrochemical sensor for deoxynivalenol.

Deoxynivalenol (DON), a mycotoxin produced by Fusarium, poses a significant risk to human health and the environment. Therefore, the development of a highly sensitive and accurate detection method is essential to monitor the pollution situation. In response to this imperative, we have devised an advanced split-type photoelectrochemical (PEC) sensor for DON analysis, which leverages self-shedding MOF-nanocarriers to modulate the photoelectric response ability of PEC substrate. The PEC sensing interface was constructed using CdS/MoSe2 heterostructures, while the self-shedding copper peroxide nanodots@ZIF-8 (CPNs@ZIF-8) served as the Cu2+ source for the in-situ ion exchange reaction, which generated a target-related signal reduction. The constructed PEC sensor exhibited a broad linear range of 0.1 pg mL-1 to 500 ng mL-1 with a low detection limit of 0.038 pg mL-1, demonstrating high stability, selectivity, and proactivity. This work not only introduces innovative ideas for the design of photosensitive materials, but also presents novel sensing strategies for detecting various environmental pollutants.

Bone fracture is associated with incident myocardial infarction in long-term follow-up.

BACKGROUND: The association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up. METHODS: A total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997-2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: From 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83-3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02-1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34-1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23-2.63, P = 0.003). CONCLUSIONS: It is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.