Clinicopathological characteristics and prognosis of uterine sarcoma: a 10-year retrospective single-center study in China.

BACKGROUND: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients. METHODS: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis. RESULTS: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS. CONCLUSION: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.

In Silico Screening of Bioactive Peptides in Stout Beer and Analysis of ACE Inhibitory Activity.

Stout beer was selected as the research object to screen angiotensin-converting enzyme (ACE) inhibitory peptides. The peptide sequences of stout beer were identified using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry with de novo, and 41 peptides were identified with high confidence. Peptide Ranker was used to score the biological activity and six peptides with a score ≥ 0.5 were screened to predict their potential ACE inhibitory (ACEI) activity. The toxicity, hydrophilicity, absorption, and excretion of these peptides were predicted. In addition, molecular docking between the peptides and ACE revealed a significant property of the peptide DLGGFFGFQR. Furthermore, molecular docking conformation and molecular dynamics simulation revealed that DLGGFFGFQR could be tightly bound to ACE through hydrogen bonding and hydrophobic interaction. Lastly, the ACEI activity of DLGGFFGFQR was confirmed using in vitro evaluation and the IC50 value was determined to be 24.45 µM.

N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia.

The mediating effect of the amygdala-frontal circuit on the association between depressive symptoms and cognitive function in Alzheimer's disease.

Depressive symptoms occur commonly in Alzheimer's disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear. We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared. Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function. We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64-97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%. Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies.

PRDX1 exerts a photoprotection effect by inhibiting oxidative stress and regulating MAPK signaling on retinal pigment epithelium.

BACKGROUND: The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism. METHODS: ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. RESULTS: After exposure to 20 mJ/cm2 intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells. CONCLUSION: PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.

Achieving pure room temperature phosphorescence (RTP) in phenoselenazine-based organic emitters through synergism among heavy atom effect, enhanced n → π* transitions and magnified electron coupling by the A-D-A molecular configuration.

The weak spin-orbit coupling (SOC) in metal-free organic molecules poses a challenge in achieving phosphorescence emission. To attain pure phosphorescence in RTP organic emitters, a promising molecular design concept has been proposed. This involves incorporating n → π* transitions and leveraging the heavy atomic effect within the spin-orbit charge transfer-induced intersystem crossing (SOCT-ISC) mechanism of bipolar molecules. Following this design concept, two bipolar metal-free organic molecules (PhSeB and PhSeDB) with donor-acceptor (D-A) and acceptor-donor-acceptor (A-D-A) configurations have been synthesized. When the molecular configuration changes from D-A to A-D-A, PhSeDB exhibits stronger electron coupling and n → π* transitions, which can further enhance the spin-orbit coupling (SOC) together with the heave atom effect from the selenium atom. By the advanced synergism among enhanced n → π* transitions, heavy atom effect and magnified electron coupling to efficiently promote phosphorescence emission, PhSeDB can achieve pure RTP emission in both the solution and doped solid film. Thanks to the higher spin-orbit coupling matrix elements (SOCMEs) for T1 ↔ S0, PhSeDB attains the highest phosphorescence quantum yield (ca. 0.78) among all the RTP organic emitters reported. Consequently, the purely organic phosphorescent light-emitting diodes (POPLEDs) based on PhSeDB achieve the highest external quantum efficiencies of 18.2% and luminance of 3000 cd m-2. These encouraging results underscore the significant potential of this innovative molecular design concept for highly efficient POPLEDs.

Actinotalea lenta sp. nov., a novel actinomycete isolated from tidal flat sediment.

Two Gram-stain-positive, aerobic, oxidase- and catalase-negative, non-motile, and short rod-shaped actinomycetes, named SYSU T00b441T and SYSU T00b490, were isolated from tidal flat sediment located in Guangdong province, PR China. The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between SYSU T00b441T and SYSU T00b490 were 99.3, 99.5 and 97.1 %, respectively. Strains SYSU T00b441T and SYSU T00b490 exhibited the highest 16S rRNA gene sequence similarities to Actinotalea ferrariae CF 5-4T (97.1 %/98.2 %), with ANI values of 74.01/73.88 % and dDDH values of 20.5/20.4 %. In the phylogenomic tree, the two isolates were affiliated with the genus Actinotalea. The genomes of strains SYSU T00b441T and SYSU T00b490 were 3.31 and 3.34 Mb, and both had DNA G+C contents of 72.8 mol%, coding 3077 and 3085 CDSs, three and three rRNA genes, and 53 and 51 tRNAs, respectively. Growth occurred at 15-40 °C (optimum, 28-30 °C), pH 4.0-10.0 (optimum, 7.0) and in the presence of 0-7 % (w/v) NaCl (optimum, 3 %). The major fatty acids (>10  %) of strains SYSU T00b441T and SYSU T00b490 were anteiso-C15 : 0 and C16 : 0. The major respiratory quinone was identified as MK-10(H4). The polar lipids of strains SYSU T00b441T and SYSU T00b490 were diphosphatidyl glycerol, phosphatidylglycerol, phosphoglycolipid, phosphatidyl ethanolamine, two phosphatidylinositol mannosides, two glycolipids and two phospholipids. Based on these data, the two strains (SYSU T00b441T and SYSU T00b490) represent a novel species of the genus Actinotalea, for which the name Actinotalea lenta sp. nov is proposed. The type strain is SYSU T00b441T (=GDMCC 1.3827T=KCTC 49943T).

[Clinical Features and Prognostic of Patients with Primary Central Nervous System Lymphoma].

OBJECTIVE: To explore the clinical features and prognosis of patients with primary central nervous system lymphoma（PCNSL）. METHODS: A retrospective analysis was performed on the relationship between clinical features, treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022. Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups. Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments, and the factors influencing survival were analyzed. RESULTS: Among 46 patients with PCNSL, which pathological type were diffuse large B-cell lymphoma（DLBCL）. There were 26(56.5%) cases of male and 20(43.5%) of female, with a median age of 54(17-71) years. In Hans subtypes, 14 cases (30.4%) of GCB subtype, 32 cases (69.6%) of non-GCB subtype. 32 cases (69.6%) of Ki-67≥80%. Among 36 patients who completed at least 2 cycles of treatment with follow-up data, the efficacy evaluation was as follows: overall response rate(ORR) was 63.9%, complete response(CR) rate was 47.2%, 17 cases of CR, 6 cases of PR. The 1-year progression-free survival rate and 1-year overall survival rate was 73.6% and 84.9%, respectively. The 2-year progression-free survival rate and 2-year overall survival rate was 52.2% and 68.9%, respectively. The ORR and CR rate of 17 patients treated with RMT regimen was 76.5% and 52.9% (9 cases CR and 4 cases PR), respectively. Univariate analysis of 3 groups of patients treated with RMT regimen, RM-BTKi regimen, and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P =0.032), and treatment regimen was associated with adverse OS in PCNSL patients（P =0.025）. CONCLUSION: Different treatment modalities were independent prognosis predictors for OS, the deep brain infiltration of PCNSL is a poor predictive factor for PFS. Patients with relapse/refractory (R/R) PCNSL have a longer overall survival time because to the novel medication BTKi. They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

Genetic Testing for Global Developmental Delay in Early Childhood.

Importance: Global developmental delay (GDD) is characterized by a complex etiology, diverse phenotypes, and high individual heterogeneity, presenting challenges for early clinical etiologic diagnosis. Cognitive impairment is the core symptom, and despite the pivotal role of genetic factors in GDD development, the understanding of them remains limited. Objectives: To assess the utility of genetic detection in patients with GDD and to examine the potential molecular pathogenesis of GDD to identify targets for early intervention. Design, Setting, and Participants: This multicenter, prospective cohort study enrolled patients aged 12 to 60 months with GDD from 6 centers in China from July 4, 2020, to August 31, 2023. Participants underwent trio whole exome sequencing (trio-WES) coupled with copy number variation sequencing (CNV-seq). Bioinformatics analysis was used to unravel pathogenesis and identify therapeutic targets. Main Outcomes and Measures: The main outcomes of this study involved enhancing the rate of positive genetic diagnosis for GDD, broadening the scope of genetic testing indications, and investigating the underlying pathogenesis. The classification of children into levels of cognitive impairment was based on the developmental quotient assessed using the Gesell scale. Results: The study encompassed 434 patients with GDD (262 [60%] male; mean [SD] age, 25.75 [13.24] months) with diverse degrees of cognitive impairment: mild (98 [23%]), moderate (141 [32%]), severe (122 [28%]), and profound (73 [17%]). The combined use of trio-WES and CNV-seq resulted in a 61% positive detection rate. Craniofacial abnormalities (odds ratio [OR], 2.27; 95% CI, 1.45-3.56), moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70), and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35) were associated with a higher risk of carrying genetic variants. Additionally, bioinformatics analysis suggested that genetic variants may induce alterations in brain development and function, which may give rise to cognitive impairment. Moreover, an association was found between the dopaminergic pathway and cognitive impairment. Conclusions and Relevance: In this cohort study of patients with GDD, combining trio-WES with CNV-seq was a demonstrable, instrumental strategy for advancing the diagnosis of GDD. The close association among genetic variations, brain development, and clinical phenotypes contributed valuable insights into the pathogenesis of GDD. Notably, the dopaminergic pathway emerged as a promising focal point for potential targets in future precision medical interventions for GDD.

Tunable intrinsic strong light-matter coupling in transition metal dichalcogenide nanoresonators.

Self-hybridizing structures based on transition metal dichalcogenides (TMDCs) are becoming promising candidates for the study of an intrinsic strong light-matter coupling because of the efficient mode overlap with much simplified geometries. However, realizing flexible tuning of intrinsic strong coupling in such TMDC-based structures is still challenging. Here, we propose a strategy for flexible tuning of the intrinsic strong light-matter coupling based on a bulk TMDC material. We report the first demonstration of the strong coupling of intrinsic excitons to whispering gallery modes (WGMs) supported by an all-TMDC nanocavity. Importantly, by simply controlling angles of incidence, a selective excitation of WGMs and an anapole can be realized, which enables a direct modulation of self-hybridized interactions from a bright WGM-exciton coupling to a dark anapole-exciton coupling. Our work is expected to provide unique opportunities for engineering a strong light-matter coupling and to open exciting avenues for highly integrated novel nanophotonic devices.

Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov., isolated from desert soil, and reclassification of Pedobacter xinjiangensis as Desertivirga xinjiangensis comb. nov. and Pedobacter mongoliensis as Paradesertivirga mongoliensis gen.nov., comb. nov.

Two novel bacterial strains, designated as SYSU D00823T and SYSU D00873T, were isolated from sandy soil of the Gurbantunggut Desert in Xinjiang, north-west China. SYSU D00823T and SYSU D00873T shared 99.0 % 16S rRNA gene sequence identity, and were both most closely related to Pedobacter xinjiangensis 12157T with 96.1 % and 96.0 % similarities, respectively. Phylogenetic and phylogenomic analyses revealed that the two isolates and P. xinjiangensis 12157T formed a separate distinct cluster in a stable subclade with the nearby species Pedobacter mongoliensis 1-32T, as well as the genera Pararcticibacter and Arcticibacter. Furthermore, P. mongoliensis 1-32T formed a separate deep-branching lineage and did not form a cluster with members of the genus Pedobacter. The average nucleotide identity and digital DNA-DNA hybridization values between SYSU D00823T and SYSU D00873T and related species were well below the thresholds for species delineation (<81.0 % and <24.0 %, respectively). The genomes of SYSU D00823T and SYSU D00873T were 6.19 and 6.43 Mbp in size with 40.4 % and 40.5 % DNA G+C contents, respectively. The predominant fatty acids (>10 %) of SYSU D00823T and SYSU D00873T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). Menaquinone-7 was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, glycosphingolipid, aminoglycolipid/glycolipid, aminophospholipid and three or four unidentified polar lipids. These data indicated that strains SYSU D00823T and SYSU D00873T should be assigned to two novel species of a new genus within the family Sphingobacteriaceae, for which the names Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov. are proposed. The type strains are SYSU D00823T (=CGMCC 1.18630T=MCCC 1K04973T=KCTC 82278T) and SYSU D00873T (=CGMCC 1.18629T=MCCC 1K04974T=KCTC 82281T), respectively. Accordingly, the reclassification of P. xinjiangensis as Desertivirga xinjiangensis comb. nov., and P. mongoliensis as Paradesertivirga mongoliensis gen. nov., comb. nov. are also proposed.

Association between the frontoparietal network, clinical symptoms and treatment response in individuals with untreated anorexia nervosa.

Background: Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN. Aims: The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN. Methods: In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline. Results: Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN. Conclusions: Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

[Specific changes in gut microbiota and short-chain fatty acid levels in infants with cow's milk protein allergy]. / ç‰›å¥¶è›‹ç™½è¿‡æ•å©´å„¿è‚ é“èŒç¾¤ç‰¹å¼‚æ€§å˜åŒ–åŠçŸ­é“¾è„‚è‚ªé ¸æ°´å¹³åˆ†æž.

OBJECTIVES: To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA. METHODS: A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites. RESULTS: Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05). CONCLUSIONS: CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.

Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.

OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.

Insights into the history and tendency of glycosylation and digestive system tumor: A bibliometric-based visual analysis.

BACKGROUND: Glycosylation, a commonly occurring post-translational modification, is highly expressed in several tumors, specifically in those of the digestive system, and plays a role in various cellular pathophysiological mechanisms. Although the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years, bibliometric analysis of this field remains scarce. The present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system tumors. AIM: To find and identify the developmental trends and research hotspots of glycosylation in digestive system tumors. METHODS: We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace (version 6.1.R6) to perform bibliometric analysis. RESULTS: A total of 2042 documents spanning from 1978 to the present were analyzed, with the research process divided into three phases: the period of obscurity (1978-1990), continuous development period (1991-2006), and the rapid outbreak period (2007-2023). These documents were authored by researchers from 66 countries or regions, with the United States and China leading in terms of publication output. Reis Celso A had the highest number of publications, while Pinho SS was the most cited author. Co-occurrence analysis revealed the most popular keywords in this field are glycosylation, expression, cancer, colorectal cancer, and pancreatic cancer. Furthermore, the Journal of Proteome Research was the most prolific journal in terms of publications, while the Journal of Biological Chemistry had the most citations. CONCLUSION: The bibliometric analysis shows current research focus is primarily on basic research in this field. However, future research should aim to utilize glycosylation as a target for treating tumor patients.

Intercorrelated Ferroelectricity and Bulk Photovoltaic Effect in Two-Dimensional Sn2P2S6 Semiconductor for Polarization-Sensitive Photodetection.

A two-dimensional (2D) ferroelectric semiconductor, which is coupled with photosensitivity and room-temperature ferroelectricity, provides the possibility of coordinated conductance modulation by both electric field and light illumination and is promising for triggering the revolution of optoelectronics for monolithic multifunctional integration. Here, we report that semiconducting Sn2P2S6 crystals can be achieved in a 2D morphology using a chemical vapor transport approach with the assistant of space confinement and experimentally demonstrate the robust ferroelectricity in atomic-thin Sn2P2S6 nanosheet at room temperature. The intercorrelated programming of ferroelectric order along out-of-plane (OOP) and in-plane (IP) directions enables a tunable bulk photovoltaic (BPV) effect through multidirectional electrical control. By combining the capability of anisotropic in-plane optical absorption, a highly integrated Sn2P2S6 optoelectronic device vertically sandwiched with graphene electrodes yields the polarization-dependent open-circuit photovoltage with a dichroic ratio of 2.0 under 405 nm light illumination. The reintroduction of ferroelectric Sn2P2S6 to the 2D asymmetric semiconductor family provides possibilities to hardware implement of the self-powered polarization-sensitive photodetection and spotlights the promising applications for next-generation photovoltaic devices.

Demographic, biochemical, clinical, and cognitive symptom differences between smokers and non-smokers in Chinese older male patients with chronic schizophrenia.

BACKGROUND: Several studies have suggested that smoking may impair cognitive function and worsen psychiatric symptoms in people with schizophrenia, but the results have not been consistent. There have been few studies to date that have examined the effects of smoking in older men with chronic schizophrenia. METHODS: The participants in our study consisted of 167 order Chinese males with chronic schizophrenia and 359 normal control subjects. We split them into smoking and non-smoking groups based on whether or not they smoked. Second, we compared their differences in terms of general demographic characteristics (such as age, education, body mass index, age of illness onset, and course of disease), disease information (such as hypertension, diabetes, and hyperlipidemia), lifestyle factors (such as physical exercise and lunch break), blood biochemical indicators (such as albumin, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein and fasting blood glucose), and medication usage (such as clozapine, olanzapine, risperidone, and chlorpromazine). Lastly, a neuropsychological test battery was used to assess their psychiatric and cognitive symptoms, for example, the Montreal Cognitive Assessment (MoCA) was used to assess their overall cognitive functioning. Their depressive symptoms were assessed by the geriatric depression scale (GDS). Activities of daily living (ADL) were used to assess their ability to lead a daily life, while the positive and negative syndrome scales (PANSS) were used to assess their psychiatric symptoms. RESULTS: Smokers who develop schizophrenia at older ages had a higher body mass index than non-smokers. We also found that plasma albumin, triglycerides, low-density lipoprotein, and fasting blood glucose concentrations were significantly higher in smokers. In contrast, smokers with schizophrenia also had lower PANSS total scores, negative symptom scores, and general psychopathology scores. A forward stepwise binary logistics regression analysis demonstrated a significant association between negative symptom scores and smoking status (B = 0.112, p < 0.001, OR = 1.119, 95% confidence interval: 1.059-1.181). Correlation analysis was carried out and it was found that the amount of cigarette consumption per day had a negative correlation with plasma albumin level(r = - 0.290, p = 0.004). However, no such association was found in normal controls. CONCLUSIONS: Elderly Chinese men with schizophrenia have a higher percentage of smokers, and although smoking can reduce their plasma albumin levels, it does contribute to the prevention of negative symptoms.

Dapagliflozin promotes white adipose tissue browning though regulating angiogenesis in high fat induced obese mice.

Browning of white adipose tissue (WAT) is become an appealing target for therapeutics in the treatment of obesity and related metabolic diseases. Dapagliflozin is widely used in the treatment of type 2 diabetes, and it is also found that the drug exhibits regulate systemic metabolism such as obesity, insulin resistance and hepatic steatosis. However, the precise role of dapagliflozin on WAT remodeling remains to be elucidated. The current study aimed to explore the role of dapagliflozin on WAT browning in high-fat diet (HFD)-induced obese mice. Male C57BL/6J mice (n = 6 per group) were used to establish obesity model by following feeding with HFD for 6 weeks. The mice were randomly treated with or without dapagliflozin for the experimental observation. The volume and fat fraction of WAT were quantified, H&E, UCP-1 staining and immunohistochemistry were conducted to investigate the white-to-brown fat conversion and angiogenesis in WAT respectively. Quantitative real-time polymerase chain reaction (qPCR) was employed to explore the mRNA expression levels of genes related to fat browning and angiogenesis in WAT. Subsequently, 3T3-L1 cells were used to explore the effect of dapagliflozin on preadipocytes differentiation in vitro. Our results demonstrated that dapagliflozin could reduce body weight gain and promote WAT browning in HFD induced obese mice via regulating lipogenesis and angiogenesis in WAT. Furthermore, dapagliflozin reduce cells differentiation, up-regulate the expression of WAT browning and angiogenesis genes in 3T3-L1 adipocytes in vitro. In conclusion, dapagliflozin can potentially promote WAT browning in HFD induced obese mice via improving lipogenesis and angiogenesis in WAT.

Molecular Twist-Induced Single-Crystal Isomerization and Valence Tautomeric Transitions in a Cobalt-Dioxolene Complex.

A mononuclear valence tautomeric (VT) complex, [Co(pycz)2(Sq)(Cat)] (1-trans), where pycz = 9-(pyridin-4-yl)-9H-carbazole, Sq⋅- = 3,5-di-tert-butyl-semiquinonato, and Cat2- = 3,5-di-tert-butyl-catecholato, is synthesized in the trans configuration, which undergoes one-step valence tautomeric transition above room temperature. Remarkably, 1-trans can transform into its isomeric structure, [Co(pycz)2(Sq)(Sq)] (1-cis), at temperature above 350 K in a single-crystal-to-single-crystal way by in situ molecular twist, and the resulting 1-cis exhibits a pronounced two-step VT transition during magnetic measurements that is rare for mononuclear VT complexes. Such drastic solid-state structural transformation is reported in VT compounds for the first time, which is actuated by a crystal surface's melting-recrystallization induced phase transition process. DFT calculations offer an underlying mechanism suggesting a concerted bond rotation during the structural transformation. The results demonstrate an unconventional approach that realizes structural transformation of VT complexes and the control of VT performance.