Single-cell sequencing of the vermiform appendix during development identifies transcriptional relationships with appendicitis in preschool children.

BACKGROUND: The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings. RESULTS: Our analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process. CONCLUSIONS: Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children.

Extramatrical mycelial biomass is mediated by fine root mass and ectomycorrhizal fungal community composition across tree species.

In many ecosystems, a large fraction of gross primary production is invested in mycorrhiza. Ectomycorrhizal (ECM) mycelium is involved in regulating soil carbon and nutrient cycling. However, little is known about how mycelial biomass, production and turnover differ depending on ECM fungal community composition and associated tree species. We quantified fine root biomass and length using soil cores, and mycelial traits (biomass, production, and turnover) using mesh-bags and ergosterol analysis, and identified ECM exploration types by Illumina MiSeq sequencing of four ECM-dominated tree species (Picea asperata, Larix gmelinii, Quercus aquifolioides and Betula albosinensis) in subalpine forest. The ECM fungal community composition separated between needle-leaved and broadleaved species, and between evergreen and deciduous species. The ratio of mycelial to fine root biomass was similar across the species regardless of genus-scale community composition and the relative abundance of exploration types. Compared to the other species, Q. aquifolioides displayed higher fine root biomass and mycelial biomass and production, dominated by contact-short exploration type. Mycelial turnover rate tended to be lowest in P. asperata, dominated by medium-long exploration type. Much higher production of mycelium and only slightly higher turnover rate in Q. aquifolioides suggests that its steady-state mycelial biomass would be higher than of the other species. Moreover, compared to the two deciduous species, with similar production but somewhat lower turnover rate, the standing crop of mycelium in P. asperata may stabilize at a higher value. Our findings, that exploration type may affect production and turnover, highlight the importance of characterizing ECM fungal communities by exploration types when estimating the contribution of mycelium biomass to forest carbon sink and storage.

Assessing the dynamics and trigger factors of drought propagation in the China-Pakistan economic corridor: A three-dimensional perspective.

Effectively managing drought in the China-Pakistan Economic Corridor (CPEC) region requires a precise understanding of the three-dimensional characteristics of meteorological drought (MD) and agricultural drought (AD), as well as the factors that trigger their propagation. This study employed non-stationary drought indices (NSPEI and SSMI) to develop a cutting-edge 3-dimensional drought identification model. This model was used to detect MD and AD patterns from 1981 to 2022 in the CPEC region and was integrated with binomial logistic regression to identify the critical factors that drive drought propagation. This study's key findings include: 1) Between 1981 and 2022, droughts in Xinjiang, China, exhibited a discernible southward migration trend, while in Pakistan, droughts showed a northward migration pattern. Drought frequency and extent have increased over time, with affected regions becoming more widespread in CPEC. Notably, drought events with higher preceding drought contagion indices (DCI) were more likely to evolve into extreme, long-term droughts. 2) Drought area emerged as a significant positive triggering factor for drought propagation in the CPEC region. Conversely, snowmelt in Xinjiang and the leaf area index for low vegetation in Pakistan acted as triggering elements affecting negatively. 3) Various factors played a pivotal role during drought propagation process, including geographical coordinates of drought centroids, DCI, and temperature variations. Additionally, snowmelt and snow evaporation significantly impacted drought propagation in Xinjiang, while vegetation cover in Pakistan played a crucial role during the drought propagation process. By utilizing four regression models and conducting comprehensive attribution analysis, this study sheds light on the characteristics of drought propagation and the factors influencing it. These findings are valuable for enhancing early warning systems and implementing effective drought mitigation strategies in the CPEC region.

Serine 3.39 and isoleucine 4.60 are key sites for 5-HT2AR-mediated Gs signaling.

Certain amino acid sites of 5-HT2AR play crucial roles in interacting with various G proteins. Hallucinogens and non-hallucinogens both act on 5-HT2AR but mediate different pharmacological effects, possibly due to the coupling of different G proteins. Therefore, this study identified the binding sites of hallucinogens and non-hallucinogens with 5-HT2AR through molecular docking. We conducted site mutation to examine the impact of these sites on G proteins, in order to find out the sites that can distinguish the pharmacological effects of hallucinogens and non-hallucinogens. Our results indicate that I4.60A and S3.39A did not affect the ability of hallucinogens to activate Gq signaling, but significantly reduced Gs signaling activation by hallucinogens. These results suggest that S3.39 and I4.60 are important for the activation of Gs signaling by hallucinogens.

Infrared laser moxibustion for cancer-related fatigue in breast cancer survivors: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

The prevalence of preterm and low birth weight infants among migrant women in the Pearl River Delta region, China: a population-based birth cohort study.

BACKGROUND: The existing literature evaluating the association between neonatal morbidity and migrant status presents contradictory results. The purpose of this study was to compare the risk of preterm birth (PTB) and low birth weight (LBW) among newborns from local and migrant women in China's Pearl River Delta (PRD) region. METHODS: In this observational population-based study, we included all live singleton deliveries from PRD region local women and migrant women. Data were sourced from the Guangdong Medical Birth Registry Information System between Jan 1, 2014, and Dec 31, 2020. Women were categorized into three groups by maternal migrant status: local women from PRD region, migrant women from Guangdong province or from other provinces. The outcome variables that were examined included two adverse birth outcomes: PTB and LBW. The association between the risk of PTB and LBW and maternal migrant status was assessed using logistic regression. RESULTS: During 2014-2020, 5,219,133 single live deliveries were recorded, corresponding 13.22% to local women and the rest to migrant women coming from Guangdong (53.51%) and other provinces (33.26%). PTB prevalence was highest among local women (5.79%), followed by migrant women from Guangdong (5.29%), and the lowest among migrants from other provinces (4.95%). This association did not change after including maternal age, infant sex, delivery mode, and birth season in the models. Compared to local women, migrant women from other provinces had a lower risk of LBW (4.00% vs. 4.98%, P < 0.001). The prevalence of PTB and LBW was higher among local women than migrants. The odds of delivery PTB and LBW were higher for women who were age ≥ 35. Among the three maternal migration groups, the age-LBW association displayed a typical U-shaped pattern, with those in the youngest (16-24 years) and oldest (≥ 35) age categories exhibiting the higher odds of delivering a LBW neonate. With respect to infant sex, the prevalence of PTB was significantly higher in males than females among the three maternal migration groups. An opposite trend was found for LBW, and the prevalence of LBW was higher in females among the three maternal migration groups. CONCLUSION: The findings of this study contribute to the understanding of the epidemiology of PTB and LBW among migrant women. Our study suggests that it is the health and robust nature of migrant mothers that predisposes them to better birth outcomes. It is important to recognize that the results of this study, while supportive of the healthy migrant effect, cannot be considered definitive without some exploration of motivation for moving and changes in lifestyle postmigration.

Echocardiographic findings and pregnancy outcomes for fetuses with complete closure of the ductus arteriosus.

OBJECTIVE: We aimed to analyze the echocardiographic characteristics and pregnancy outcomes for fetuses with premature complete closure of the fetal ductus arteriosus. METHODS: A retrospective analysis was performed for eight cases of premature ductus arteriosus closure diagnosed by prenatal ultrasonography in the Hunan Maternal and Child Health Hospital from July 2019 to August 2022, and the characteristics of fetal echocardiography and pregnancy outcomes of the eight cases were analyzed and summarized. RESULTS: In all cases, the intima of the ductus arteriosus was thickened and occluded, the ductus arteriosus could be seen with slightly hyperechogenic, and no blood flow signal was found in the ductus arteriosus by Doppler ultrasonography. The right heart was enlarged in seven cases, and the whole heart was enlarged in one case. Tricuspid valve regurgitation was observed to different degrees, of which seven cases were severe and one case was moderate. The pulmonary arteries of eight patients had varying degrees of widening. All eight cases were delivered by cesarean section, and one newborn died after follow-up. The prognosis of the other newborns was good. CONCLUSION: The parameters of prenatal echocardiography are helpful for the prognosis of fetuses with premature closure of the ductus arteriosus. Early prenatal detection, close observation, and clinical guidance can be used to select the right time of delivery.

Effects of light qualities on growth and physiological-biochemical traits of Scutellaria baicalensis.

Canopy spectral composition significantly affects growth and functional traits of understory plants. In this study, we explored the optimal light condition suitable for enhancing Scutellaria baicalensis's yield and quality, aiming to provide scientific reference for the exploitation and utilization of medicinal plant resources in the understory of forests. We measured the responses of growth, morphology, biomass allocation, physiological traits, and secon-dary metabolites of S. baicalensis to different light qualities. S. baicalensis was cultured under five LED-light treatments including full spectrum light (control), ultraviolet-A (UV-A) radiation, blue, green, and red light. Results showed that UV-A significantly reduced plant height, base diameter, leaf thickness, leaf area ratio, and biomass of each organ. Red light significantly reduced base diameter, biomass, effective quantum yield of photosystem Ⅱ (ФPSⅡ), and total flavonoid concentration. Under blue light, root length and total biomass of S. baicalensis significantly increased by 48.0% and 10.8%, respectively, while leaf number and chlorophyll content significantly decreased by 20.0% and 31.6%, respectively. The other physiological and biochemical traits were consistent with their responses in control. Our results suggested that blue light promoted photosynthesis, biomass accumulation, and secondary metabolite synthesis of S. baicalensis, while red light and UV-A radiation negatively affected physiological and biochemical metabolic processes. Therefore, the ratio of blue light could be appropriately increased to improve the yield and quality of S. baicalensis.

Optimizing biochar application for enhanced cotton and sugar beet production in Xinjiang: a comprehensive study.

BACKGROUND: Optimizing biochar application is vital for enhancing crop production and ensuring sustainable agricultural production. A 3-year field experiment was established to explore the effects of varying the biochar application rate (BAR) on crop growth, quality, productivity and yields. BAR was set at 0, 10, 50 and 100 t ha-1 in 2018; 0, 10, 25, 50 and 100 t ha-1 in 2019; and 0, 10, 25 and 30 t ha-1 in 2020. Crop quality and growth status and production were evaluated using the dynamic technique for order preference by similarity to ideal solution with the entropy weighted method (DTOPSIS-EW), principal component analysis (PCA), membership function analysis (MFA), gray relation analysis (GRA) and the fuzzy Borda combination evaluation method. RESULTS: Low-dose BAR (≤ 25 t ha-1 for cotton; ≤ 50 t ha-1 for sugar beet) effectively increased biomass, plant height, leaf area index (LAI), water and fertility (N, P and K) productivities, and yield. Biochar application increased the salt absorption and sugar content in sugar beet, with the most notable increases being 116.45% and 20.35%, respectively. Conversely, BAR had no significant effect on cotton fiber quality. The GRA method was the most appropriate for assessing crop growth and quality. The most indicative parameters for reflecting cotton and sugarbeet growth and quality status were biomass and LAI. The 10 t ha-1 BAR consistently produced the highest scores and was the most economically viable option, as evaluated by DTOPSIS-EW. CONCLUSION: The optimal biochar application strategy for improving cotton and sugar beet cultivation in Xinjiang, China, is 10 t ha-1 biochar applied continuously. © 2024 Society of Chemical Industry.

The potential mechanism of Aidi injection against neuroblastoma-an investigation based on network pharmacology analysis.

Background: Aidi injection, a classic traditional Chinese medicine (TCM) formula, has been used on a broader scale in treating a variety of cancers. In this study, we aimed to explore the potential anti-tumor effects of Aidi injection in the treatment of neuroblastoma (NB) using network pharmacology (NP). Methods: To elucidate the anti-NB mechanism of Aidi injection, an NP-based approach and molecular docking validation were employed. The compounds and target genes were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database. The protein-protein interaction network was constructed using the STRING database. clusterProfiler (R package) was utilized to annotate the bioinformatics of hub target genes. The gene survival analysis was performed on R2, a web-based genomic analysis application. iGEMDOCK was used for molecular docking validation, and GROMACS was utilized to validate molecular docking results. Furthermore, we investigated the anticancer effects of gomisin B and ginsenoside Rh2 on human NB cells using a cell viability assay. The Western blot assay was used to validate the protein levels of target genes in gomisin B- and ginsenoside Rh2-treated NB cells. Results: A total of 2 critical compounds with 16 hub target genes were identified for treating NB. All 16 hub genes could potentially influence the survival of NB patients. The top three genes (EGFR, ESR1, and MAPK1) were considered the central hub genes from the drug-compound-hub target gene-pathway network. The endocrine resistance and estrogen signaling pathways were identified as the therapeutic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gomisin B and ginsenoside Rh2 showed a good binding ability to the target protein in molecular docking. The results of cell experiments showed the anti-NB effect of gomisin B and ginsenoside Rh2. In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells. Conclusion: In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research.

Postnatal treatment and evolution patterns of giant fetal hepatic hemangioma: a case series of 29 patients.

OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.

Lenvatinib, sintilimab plus transarterial chemoembolization for advanced stage hepatocellular carcinoma: A phase II study.

BACKGROUND & AIMS: Our retrospective study has suggested encouraging outcomes of lenvatinib combined with PD-1 inhibitor and transarterial chemoembolization (TACE) on advanced hepatocellular carcinoma (HCC). This phase II trial was conducted to prospectively investigate the efficacy and safety of lenvatinib, sintilimab (a PD-1 inhibitor) plus TACE (Len-Sin-TACE) in patients with advanced stage HCC. METHODS: This was a single-arm phase II trial. Patients with BCLC stage C HCC were recruited. They received lenvatinib (bodyweight ≥60 kg, 12 mg; bodyweight <60 kg, 8 mg) orally once daily, sintilimab (200 mg) intravenously once every 3 weeks, and on demand TACE. The primary endpoint was progression-free survival (PFS) per mRECIST. RESULTS: Thirty patients were enrolled. The primary endpoint was met with a median PFS of 8.0 (95% confidence interval [CI]: 6.1-9.8) months per mRECIST, which was the same as that per RECIST 1.1. The objective response rate was 60.0% per mRECIST and 30.0% per RECIST 1.1. The disease control rate was 86.7% per mRECIST/RECIST 1.1. The median duration of response was 7.4 (95% CI: 6.6-8.2) months per mRECIST (n = 18) and 4.3 (95% CI: 4.0-4.6) months per RECIST 1.1 (n = 9). The median overall survival was 18.4 (95% CI: 14.5-22.3) months. Treatment-related adverse events (TRAEs) occurred in 28 patients (93.3%) and grade 3 TRAEs were observed in 12 patients (40.0%). There were no grade 4/5 TRAEs. CONCLUSIONS: Len-Sin-TACE showed promising antitumour activities with a manageable safety profile in patients with advanced stage HCC. The preliminary results need to be further evaluated with phase III randomized trials.

Modulation of DOM-Induced Head-Twitch Response by mGluR2 Agonist/Inverse Agonist is Associated with 5-HT2AR-Mediated Gs Signaling Pathway.

Hallucinogenic 5-HT2A receptor (5-HT2AR) agonists-induced head-twitch response (HTR) is regulated by Gs signaling pathway. Formation of heterodimers between 5-HT2AR and metabotropic glutamate mGlu2 receptor (mGluR2) is essential for the hallucinogenic 5-HT2AR agonist-induced HTR. In order to investigate the effects of mGluR2 agonists and inverse agonists on hallucinogenic 5-HT2AR agonists DOM-induced HTR, C57BL/6 mice were pretreated with mGluR2 agonists (LY379268, LY354740, LY404039) or the inverse agonist LY341495, and the HTR was manually counted after administering DOM immediately. IP-One (IP1) HTRF assay and cAMP assay were performed to evaluate the effect of LY341495 or LY354740 on DOM-induced Gq and Gs activation in Human Embryonic Kidney-293 (HEK-293) T-type cells co-expressing 5-HT2AR and mGluR2. The results showed that DOM-induced HTR in mice was dose-dependently inhibited by LY379268, LY354740, and LY404039, while it was dose-dependently enhanced by LY341495. Moreover, LY341495 reversed the inhibitory effect of LY354740 on DOM-induced HTR. In HEK-293T cells co-expressing 5-HT2AR and mGluR2, DOM-induced cAMP level was decreased by LY354740 and increased by LY341495, but DOM-induced IP1 level was not regulated by LY354740 or LY341495. The regulation of DOM-induced HTR by mGluR2 agonists and inverse agonists is closely related to 5-HT2AR-mediated Gs signaling pathway. In HEK-293T cells co-expressing 5-HT2AR and mGluR2 A677S/A681P/A685G mutant (mGluR2 3 A mutant), DOM-induced cAMP level was not regulated by LY354740, but was significantly enhanced by LY341495. The 5-HT2AR/mGluR2 heterodimers is critical for DOM-induced HTR and cAMP level, both of which are inhibited by mGluR2 agonists and enhanced by mGluR2 inverse agonists.

Microbiota-indole 3-propionic acid-brain axis mediates abnormal synaptic pruning of hippocampal microglia and susceptibility to ASD in IUGR offspring.

BACKGROUND: Autism spectrum disorder (ASD) has been associated with intrauterine growth restriction (IUGR), but the underlying mechanisms are unclear. RESULTS: We found that the IUGR rat model induced by prenatal caffeine exposure (PCE) showed ASD-like symptoms, accompanied by altered gut microbiota and reduced production of indole 3-propionic acid (IPA), a microbiota-specific metabolite and a ligand of aryl hydrocarbon receptor (AHR). IUGR children also had a reduced serum IPA level consistent with the animal model. We demonstrated that the dysregulated IPA/AHR/NF-κB signaling caused by disturbed gut microbiota mediated the hippocampal microglia hyperactivation and neuronal synapse over-pruning in the PCE-induced IUGR rats. Moreover, postnatal IPA supplementation restored the ASD-like symptoms and the underlying hippocampal lesions in the IUGR rats. CONCLUSIONS: This study suggests that the microbiota-IPA-brain axis regulates ASD susceptibility in PCE-induced IUGR offspring, and supplementation of microbiota-derived IPA might be a promising interventional strategy for ASD with a fetal origin. Video Abstract.

The effect of NK cell therapy on sepsis secondary to lung cancer: A case report.

Patients with sepsis face high mortality rates and a bleak prognosis, prompting the need for advanced therapeutic interventions. A male patient diagnosed with moderately low-differentiated squamous cell carcinoma received diverse treatments, including radiotherapy, chemotherapy, immunotherapy, and targeted therapy to inhibit angiogenesis. Subsequently, he developed sepsis after comprehensive treatment, and conventional antibiotic combinations proved ineffective in combating the infection. As an experimental approach, allogeneic natural killer (NK) cell infusion was administered. Following the NK cell infusion, the patient regained consciousness, and laboratory analyses showed reduced infection-related markers, suppressed serum inflammatory cytokines, and elevated anti-tumor cytokines. However, the therapeutic effect only lasted 2-3 days. In vitro investigations demonstrated that the allogeneic NK cell product reduced interleukin-6 levels in the patient's serum. Moreover, subsequent co-cultivation of the NK cell product with the patient's serum resulted in a decrease in the proportion of cytotoxic subpopulations of NK cells and a downregulation of the expression of NK-mediated killing molecules. In conclusion, adoptive transfusion of allogeneic NK cells may improve sepsis symptoms in patients with tumor-related sepsis. In vitro co-culture tests hold promise in providing predictive biomarkers for treatment effectiveness.

Fecal Microbiota Underlying the Coexistence of Schizophrenia and Multiple Sclerosis in Chinese Patients.

Both schizophrenia (SZ) and multiple sclerosis (MS) affect millions of people worldwide and impose a great burden on society. Recent studies indicated that MS elevated the risk of SZ and vice versa, whereas the underlying pathological mechanisms are still obscure. Considering that fecal microbiota played a vital role in regulating brain functions, the fecal microbiota and serum cytokines from 90 SZ patients and 71 age-, gender-, and BMI-matched cognitively normal subjects (referred as SZC), 22 MS patients and 33 age-, gender-, and BMI-matched healthy subjects (referred as MSC) were analyzed. We found that both diseases demonstrated similar microbial diversity and shared three differential genera, including the down-regulated Faecalibacterium, Roseburia, and the up-regulated Streptococcus. Functional analysis indicated that the three genera were involved in pathways such as "carbohydrate metabolism" and "amino acid metabolism." Moreover, the variation patterns of serum cytokines associated with MS and SZ patients were a bit different. Among the six cytokines perturbed in both diseases, TNF-α increased, while IL-8 and MIP-1α decreased in both diseases. IL-1ra, PDGF-bb, and RANTES were downregulated in MS patients but upregulated in SZ patients. Association analyses showed that Faecalibacterium demonstrated extensive correlations with cytokines in both diseases. Most notably, Faecalibacterium correlated negatively with TNF-α. In other words, fecal microbiota such as Faecalibacterium may contribute to the coexistence of MS and SZ by regulating serum cytokines. Our study revealed the potential roles of fecal microbiota in linking MS and SZ, which paves the way for developing gut microbiota-targeted therapies that can manage two diseases with a single treat.

Gestational dexamethasone exposure impacts hippocampal excitatory synaptic transmission and learning and memory function with transgenerational effects.

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Extreme temperature exposure increases the risk of preterm birth in women with abnormal pre-pregnancy body mass index: a cohort study in a southern province of China.

Background: Prior literature has found that extreme temperature exposure is associated with preterm birth (PTB). However, current evidence provides heterogeneous conclusions, and data on extreme cold and across different pre-pregnancy body mass index (BMI) statuses are limited. Methods: We conducted a population-based retrospective cohort of 251,257 women between 2014 and 2017 in Guangdong, China, to evaluate whether the association between extreme temperature exposure and PTB varied in pre-pregnancy BMI status. Participants were divided into three categories based on pre-pregnancy BMI: underweight (BMI < 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), overweight or obesity (≥ 24.0 kg/m2). We fitted Cox proportional hazards models to assess the association between daily mean temperature and PTB at each trimester for each BMI category separately. The hazard ratios (HRs) at the 5th and 95th percentiles of temperature (defined as low and high temperatures respectively) were provided using the median temperature at each trimester as a reference. Results: 58,220 (23.2%) were underweight, and 27,865 (11.1%) were overweight or obese. Of the 251,257 women, 18,612 (7.41%) had PTB delivery. Both low-and high-temperature exposure increased the risk of PTB in the third trimester, while cold exposure mostly mitigated the risk for the first and second trimesters. The association with low temperature was the strongest in the third trimester, especially for underweight women (HR: 1.825; 95%CI: 1.529 ~ 2.179), while the association with high temperature was the strongest also in the third trimester, especially for obese or overweight women (HR:1.825; 95%CI:1.502 ~ 2.218). Furthermore, the attributable fractions of PTB risk in the third trimester were estimated as 5.59% (95% CI: 3.58, 7.98%) for cold exposure among underweight women and 3.31% (95% CI: 2.01, 4.88%) for hot exposure among overweight or obese women. Conclusion: Exposure to either low temperature in the third trimester or high temperature during pregnancy was associated with a higher risk of PTB. Moreover, pre-pregnancy BMI status might affect the susceptibility of pregnant women. Such findings would be useful to develop targeted measures for vulnerable populations.