Constructing Photocatalytic Covalent Organic Frameworks with Aliphatic Linkers.

Photocatalytic covalent organic frameworks (COFs) are typically constructed with rigid aromatic linkers for crystallinity and extended π-conjugation. However, the essential hydrophobicity of the aromatic backbone can limit their performances in water-based photocatalytic reactions. Here, we for the first time report the synthesis of hydrophilic COFs with aliphatic linkers [tartaric acid dihydrazide (TAH) and butanedioic acid dihydrazide] that can function as efficient photocatalysts for H2O2 and H2 evolution. In these hydrophilic aliphatic linkers, the specific multiple hydrogen bonding networks not only enhance crystallization but also ensure an ideal compatibility of crystallinity, hydrophilicity, and light harvesting. The resulting aliphatic linker COFs adopt an unusual ABC stacking, giving rise to approximately 0.6 nm nanopores with an improved interaction with water guests. Remarkably, both aliphatic linker-based COFs show strong visible light absorption, along with a narrow optical band gap of ∼1.9 eV. The H2O2 evolution rate for TAH-COF reaches up to 6003 µmol h-1 g-1, in the absence of sacrificial agents, surpassing the performance of all previously reported COF-based photocatalysts. Theoretical calculations reveal that the TAH linker can enhance the indirect two-electron oxygen reduction reaction for H2O2 production by improving the O2 adsorption and stabilizing the *OOH intermediate. This study opens a new avenue for constructing semiconducting COFs using nonaromatic linkers.

Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins.

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as a straightforward and efficient tool for stereoselectively forging C-C bond. Nevertheless, the creation of acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within the domain of cross-coupling chemistry despite their prominence in various bioactive small molecules. Herein, we describe a palladium-catalyzed asymmetric multicomponent cross-coupling of trisubstituted alkene with aryl diazonium salts and arylboronic acids to realize the formation of tertiary-quaternary carbon centers with high regio-, distereo-, and enantioselectivity. Specifically, the precise manipulation of the stereoconfiguration of trisubstituted alkenes enables the divergent stereoselective cross-coupling reaction, thus allowing for the facile construction of all four enantiomers. Harnessing the ligand-swap strategy involving a chiral bisoxazoline and an achiral fumarate individually accelerates the enantioselective migratory insertion and reductive elimination step in the cross-coupling process, as supported by density functional theory (DFT) calculations, thus obviating the requirement for a neighboring directing group within the internal olefin skeleton.

The Oncolytic virus VT1092M and an Anti-PD-L1 antibody synergize to induce systemic antitumor immunity in a murine bilateral tumor model.

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.

Terpene synthases GhTPS6 and GhTPS47 participate in resistance to Verticillium dahliae in upland cotton.

Terpene synthases (TPSs) are enzymes responsible for catalyzing the production of diverse terpenes, the largest class of secondary metabolites in plants. Here, we identified 107 TPS gene loci encompassing 92 full-length TPS genes in upland cotton (Gossypium hirsutum L.). Phylogenetic analysis showed they were divided into six subfamilies. Segmental duplication and tandem duplication events contributed greatly to the expansion of TPS gene family, particularly the TPS-a and TPS-b subfamilies. Expression profile analysis screened out that GhTPSs may mediate the interaction between cotton and Verticillium dahliae. Three-dimensional structures and subcellular localizations of the two selected GhTPSs, GhTPS6 and GhTPS47, which belong to the TPS-a subfamily, demonstrated similarity in protein structures and nucleus and cytoplasm localization. Virus-induced gene silencing (VIGS) of the two GhTPSs yielded plants characterized by increased wilting and chlorosis, more severe vascular browning, and higher disease index than control plants. Additionally, knockdown of GhTPS6 and GhTPS47 led to the down-regulation of cotton terpene synthesis following V. dahliae infection, indicating that these two genes may positively regulate resistance to V. dahliae through the modulation of disease-resistant terpene biosynthesis. Overall, our study represents a comprehensive analysis of the G. hirsutum TPS gene family, revealing their potential roles in defense responses against Verticillium wilt.

A polysaccharide PRCP from Rosa cymosa Tratt fruit: Structural characteristics and immunomodulatory effects via MAPK pathway modulation in vitro.

The Rosa cymosa Tratt, an herbal plant from the Rosaceae family, has historically been valued in China for its medicinal and edible properties. In this study, a novel polysaccharide from R. cymosa fruit, termed PRCP (purified R. cymosa polysaccharide), was isolated using water extraction, decolorization, deproteinization, and ion-exchange chromatography. The structural characteristics of PRCP were investigated using monosaccharide composition analysis, methylation, GPC, FTIR, CD, and NMR spectroscopy. The immunomodulatory effect and potential mechanism of PRCP were evaluated in vitro using a macrophage cell model. Results indicated that PRCP (37.28 kDa) is a highly branched polysaccharide (72.61 %) primarily composed of arabinogalactan, rhamnogalacturonan, and galactoglucan domains with 13 types of glycosidic linkage fragments. Furthermore, PRCP appears to modulate immunomodulatory effects by influencing the phosphorylation of P38 and JNK proteins in the MAPK pathway. Collectively, these findings highlight the potential of PRCP as a promising natural functional food ingredient for immunostimulation.

Nobiletin Protects Against Alcoholic Liver Disease in Mice via the BMAL1-AKT-Lipogenesis Pathway.

SCOPE: Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD. METHODS AND RESULTS: This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1flox/flox and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1flox/flox mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1flox/flox mice. Nobiletin antagonizes the expression of these genes in Bmal1flox/flox mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner. CONCLUSION: Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.

ERß activation improves nonylphenol-induced depression and neurotransmitter secretion disruption via the TPH2/5-HT pathway.

The aim of this study is to investigate the role of estrogen receptor ß (ERß) in nonylphenol (NP) - induced depression - like behavior in rats and its impact on the regulation of the TPH2/5-HT pathway. In the in vitro experiment, rat basophilic leukaemia cells (RBL-2H3) cells were divided into the four groups: blank group, NP group (20 µM), ERß agonist group (0.01 µM), and NP＋ERß agonist group (20 µM＋0.01 µM). For the in vivo experiment, 72 adult male Sprague-Dawley rats were randomly divided into following six groups: the Control, NP (40 mg/kg) group, ERß agonist (2 mg/kg, Diarylpropionitrile (DPN)) group, ERß inhibitor (0.1 mg/kg, 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl) phenol (PHTPP)) group, NP+ERß agonist (40 mg/kg NP ＋ 2 mg/kg DPN) group, and NP+ERß inhibitor (40 mg/kg NP + 0.1 mg/kg PHTPP) group, with 12 rats in each group. Each rat in drug group were given NP by gavage and/or received a single intraperitoneal injection of DPN 2 mg/kg or PHTPP 0.1 mg/kg. Both in vivo and in vitro, NP group showed a decrease in the expression levels of ERß, tryptophan hydroxylase (TPH1), and tryptophan hydroxylase-2 (TPH2) genes and proteins, and reduced levels of DA, NE, and 5-hydroxytryptophan (5-HT) neurotransmitters. RBL-2H3 cells showed signs of cell shrinkage, with rounded cells, increased suspension and more loosely arranged cells. The effectiveness of the ERß agonist stimulation exhibited an increase exceeding 60% in RBL-2H3 cells. The application of ERß agonist resulted in an alleviation the aforementioned alterations. ERß agonist activated the TPH2/5-HT signaling pathways. Compared to the control group, the NP content in the brain tissue of the NP group was significantly increased. The latency to eat for the rats was longer and the amount of food consumed was lower, and the rats had prolonged immobility time in the behavioral experiment of rats. The expression levels of ERß, TPH1, TPH2, 5-HT and 5-HITT proteins were decreased in the NP group, suggesting NP-induced depression-like behaviours as well as disturbances in the secretion of serum hormones and monoamine neurotransmitters. In the NP group, the midline raphe nucleus showed an elongated nucleus with a dark purplish-blue colour, nuclear atrophy, displacement and pale cytoplasm. ERß might ameliorate NP-induced depression-like behaviors, and secretion disorders of serum hormones and monoamine neurotransmitters via activating TPH2/5-HT signaling pathways.

Severe dawn phenomenon predicts long-term risk of all-cause mortality in patients with type 2 diabetes.

AIMS: The dawn phenomenon (DP) is an abnormal early morning blood glucose rise without nocturnal hypoglycaemia, which can be more easily and precisely assessed with continuous glucose monitoring (CGM). This prospective study aimed to explore the association between DP and the risk of all-cause mortality in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 5542 adult inpatients with type 2 diabetes in a single centre were analysed. The magnitude of DP (ΔG) was defined as the increment in the CGM-determined glucose value from nocturnal nadir (after 24:00) to prebreakfast. Participants were stratified into four groups by ΔG: ≤1.11, 1.12-3.33, 3.34-5.55, and >5.55 mmol/L. Cox proportional hazard regression models were used to evaluate the impact of DP on all-cause mortality risk. RESULTS: During a median follow-up of 9.4 years, 1083 deaths were identified. The restricted cubic spline revealed a nonlinear (p for nonlinearity = 0.002) relationship between ΔG and the risk of all-cause mortality. A multivariate-adjusted Cox regression model including glycated haemoglobin A1c (HbA1c) showed that ΔG > 5.55 mmol/L was associated with 30% (95% CI, 1.01-1.66) higher risk of all-cause mortality, as compared with ΔG 1.12-3.33 mmol/L. CONCLUSIONS: Higher ΔG is significantly related to an increased risk of all-cause mortality in type 2 diabetes, suggesting that severe DP should be given more attention as a part of glucose management to reduce the risk of long-term adverse outcomes.

Multivariate Silicification-Assisted Single Enzyme Structure Augmentation for Improved Enzymatic Activity-Stability Trade-Off.

The ability to finely tune/balance the structure and rigidity of enzymes to realize both high enzymatic activity and long-term stability is highly desired but highly challenging. In this work, we propose a new concept of silica-enzyme, referred to as "silicazyme", where solid inorganic silica was controlled hybridization with fragile enzyme under moderate condition at single-enzyme level, realizing simultaneous structure augmentation, long-term stability, and high enzymatic activity preservation. A multivariate silicification approach was utilized and occurred around individual enzymes to allow conformal coating. To realize a high activity-stability trade-off the structure flexibility/rigidity of silicazyme was optimized by a component-adjustment-ternary (CAT) plot method. Moreover, the multivariate organosilica frameworks bring great advantages including surface microenvironment adjustability, reversible modification capability, and functional extensibility through the rich chemistry of silica. Overall silicazymes represent a new class of enzymes that promise to broaden their utilization in catalysis, separations, and nanomedicine.

Critical roles and clinical perspectives of RNA methylation in cancer.

RNA modification, especially RNA methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all RNA modifications. It plays a significant role in RNA metabolism, affecting RNA processing, stability, and translation, thereby modulating gene expression and cell functions essential for proliferation, survival, and metastasis. Increasing studies have revealed the disruption in RNA metabolism mediated by RNA methylation has been implicated in various aspects of cancer progression, particularly in metabolic reprogramming and immunity. This disruption of RNA methylation has profound implications for tumor growth, metastasis, and therapy response. Herein, we elucidate the fundamental characteristics of RNA methylation and their impact on RNA metabolism and gene expression. We highlight the intricate relationship between RNA methylation, cancer metabolic reprogramming, and immunity, using the well-characterized phenomenon of cancer metabolic reprogramming as a framework to discuss RNA methylation's specific roles and mechanisms in cancer progression. Furthermore, we explore the potential of targeting RNA methylation regulators as a novel approach for cancer therapy. By underscoring the complex mechanisms by which RNA methylation contributes to cancer progression, this review provides a foundation for developing new prognostic markers and therapeutic strategies aimed at modulating RNA methylation in cancer treatment.

Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

Effect of Carbamazepine on the Pharmacokinetics of Erdafitinib in Healthy Participants.

Erdafitinib, a selective and potent oral pan-FGFR inhibitor, is metabolized mainly through CYP2C9 and CYP3A4 enzymes. This phase 1, open-label, single-sequence, drug-drug interaction study evaluated the pharmacokinetics, safety, and tolerability of a single oral dose of erdafitinib alone and when co-administered with steady state oral carbamazepine, a dual inducer of CYP3A4 and CYP2C9, in 13 healthy adult participants (NCT04330248). Compared with erdafitinib administration alone, carbamazepine co-administration decreased total and free maximum plasma concentrations of erdafitinib (Cmax) by 35% (95% CI 30%-39%) and 22% (95% CI 17%-27%), respectively. The areas under the concentration-time curve over the time interval from 0 to 168 hours, to the last quantifiable data point, and to time infinity (AUC168h, AUClast, AUCinf), were markedly decreased for both total erdafitinib (56%-62%) and free erdafitinib (48%-55%). The safety profile of erdafitinib was consistent with previous clinical studies in healthy participants, with no new safety concerns when administered with or without carbamazepine. Co-administration with carbamazepine may reduce the activity of erdafitinib due to reduced exposure. Concomitant use of strong CYP3A4 inducers with erdafitinib should be avoided.

Influence of physical exercise on negative emotions in college students: chain mediating role of sleep quality and self-rated health.

Background: Negative emotions in college students are a significant factor affecting mental health, with suicide behaviors caused by negative emotions showing an annual increasing trend. Existing studies suggest that physical exercise is essential to alleviate negative feelings, yet the intrinsic mechanisms by which it affects negative emotions have not been fully revealed. Objective: Negative emotions in college students represent a significant issue affecting mental health. This study investigates the relationship between physical exercise and negative emotions among college students, incorporating sleep quality and self-rated health (SRH) as mediators to analyze the pathway mechanism of how physical exercise affects students' negative emotions. Methods: A cross-sectional study design was utilized, employing online questionnaires for investigation. The scales included the Physical Activity Rating Scale-3 (PARS-3), the Depression Anxiety Stress Scales-21 (DASS-21), the Pittsburgh Sleep Quality Index (PSQI), and the 12-Item Short Form Health Survey (SF-12), resulting in the collection of 30,475 valid questionnaires, with a validity rate of 91%. Chain mediation tests and Bootstrap methods were applied for effect analysis. Results: The proportions of university students engaged in low, medium, and high levels of physical exercise were 77.6, 13.1, and 9.3%, respectively. The proportions of students experiencing "very severe" levels of stress, anxiety, and depression were 4.5, 10.9, and 3.6%, respectively. Physical exercise was significantly positively correlated with self-rated health (r = 0.194, p < 0.01), significantly negatively correlated with sleep quality (r = -0.035, p < 0.01), and significantly negatively correlated with stress, anxiety, and depression (r = -0.03, p < 0.01; r = -0.058, p < 0.01; r = -0.055, p < 0.01). Sleep quality was significantly negatively correlated with self-rated health (r = -0.242, p < 0.01). Mediation effect testing indicated that sleep quality and self-rated health partially mediated the relationship between physical exercise and negative emotions, with total effect, total direct effect, and total indirect effect values of -1.702, -0.426, and - 1.277, respectively. Conclusion: College students primarily engage in low-intensity physical activity. Sleep quality and self-rated health mediate the impact of physical exercise on students' negative emotions. A certain level of physical activity can directly affect students' emotional states and indirectly influence their negative emotions via sleep and self-rated health. Regular engagement in physical activities primarily positively impacts emotional states by enhancing mood stability and overall emotional resilience.

GSH-Responsive Liposomes with Heat Shock Protein Regulatory Ability for Efficient Photodynamic/Photothermal Combined Therapy of Tumors.

Phototherapy, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), has great potential in tumor treatment. However, the presence of antioxidant glutathione (GSH) and the heat shock proteins (HSPs) expression caused by high temperature can weaken the effects of PDT and PTT. Here, a multifunctional nanocomplex BT&GA@CL is constructed to realize enhanced synergistic PDT/PTT. Cinnamaldehyde liposomes (CLs) formed by cinnamaldehyde dimer self-assembly were loaded with in gambogic acid (GA) and an aggregation-induced emission molecule BT to obtain BT&GA@CL. As a drug carrier, CL can consume glutathione (GSH) and release drugs responsively. The released BT aggregates can simultaneously act as both a photothermal agent and photosensitizer to achieve PDT and PTT under 660 nm laser irradiation. Specifically, GA as an HSP90 inhibitor can attenuate PTT-induced HSP90 protein expression, thereby weakening the tolerance of tumor cells to high temperatures and enhancing PTT. Such a multifunctional nanocomplex simultaneously modulates the content of GSH and HSP90 in tumor cells, thus enhancing both PDT and PTT, ultimately achieving the goal of efficient combined tumor suppression.

The GATAD2B-NuRD complex drives DNA:RNA hybrid-dependent chromatin boundary formation upon DNA damage.

Double-strand breaks (DSBs) are the most lethal form of DNA damage. Transcriptional activity at DSBs, as well as transcriptional repression around DSBs, are both required for efficient DNA repair. The chromatin landscape defines and coordinates these two opposing events. However, how the open and condensed chromatin architecture is regulated remains unclear. Here, we show that the GATAD2B-NuRD complex associates with DSBs in a transcription- and DNA:RNA hybrid-dependent manner, to promote histone deacetylation and chromatin condensation. This activity establishes a spatio-temporal boundary between open and closed chromatin, which is necessary for the correct termination of DNA end resection. The lack of the GATAD2B-NuRD complex leads to chromatin hyperrelaxation and extended DNA end resection, resulting in homologous recombination (HR) repair failure. Our results suggest that the GATAD2B-NuRD complex is a key coordinator of the dynamic interplay between transcription and the chromatin landscape, underscoring its biological significance in the RNA-dependent DNA damage response.

Identification of candidate genes for adult plant stripe rust resistance transferred from Aegilops ventricosa 2NvS into wheat via fine mapping and transcriptome analysis.

KEY MESSAGE: An adult plant gene for resistance to stripe rust was narrowed down to the proximal one-third of the 2NvS segment translocated from Aegilops ventricosa to wheat chromosome arm 2AS, and based on the gene expression analysis, two candidate genes were identified showing a stronger response at the adult plant stage compared to the seedling stage. The 2NvS translocation from Aegilops ventricosa, known for its resistance to various diseases, has been pivotal in global wheat breeding for more than three decades. Here, we identified an adult plant resistance (APR) gene in the 2NvS segment in wheat line K13-868. Through fine mapping in a segregating near-isogenic line (NIL) derived population of 6389 plants, the candidate region for the APR gene was narrowed down to between 19.36 Mb and 33 Mb in the Jagger reference genome. Transcriptome analysis in NILs strongly suggested that this APR gene conferred resistance to stripe rust by triggering plant innate immune responses. Based on the gene expression analysis, two disease resistance-associated genes within the candidate region, TraesJAG2A03G00588940 and TraesJAG2A03G00590140, exhibited a stronger response to Puccinia striiformis f. sp. tritici (Pst) infection at the adult plant stage than at the seedling stage, indicating that they could be potential candidates for the resistance gene. Additionally, we developed a co-dominant InDel marker, InDel_31.05, for detecting this APR gene. Applying this marker showed that over one-half of the wheat varieties approved in 2021 and 2022 in Sichuan province, China, carry this gene. Agronomic trait evaluation of NILs indicated that the 2NvS segment effectively mitigated the negative effects of stripe rust on yield without affecting other important agronomic traits. This study provided valuable insights for cloning and breeding through the utilization of the APR gene present in the 2NvS segment.

The role of FERMT2 in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

Umbilical Cord Blood and UC-MSCs Combined with Low-Dose Immunosuppressant in the Treatment of Elderly Patients with Pure Red Cell Aplastic: A Case Series.

INTRODUCTION: At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare. CASE PRESENTATION: In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable. CONCLUSION: This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

Public attitudes toward COVID-19 prevention and control in China.

Based on the data of the Chinese General Social Survey (CGSS) in 2021, this study aims to investigate the public attitudes toward COVID-19 prevention and control in China. The household survey CGSS 2021 contains 8,148 valid samples gathered from 320 communities across 19 provinces in China. The logistic regression model is adopted to examine the relationship between public attitudes and influencing factors. The results show that the vast majority of respondents firmly believe that the government has the authority to implement strict measures; their confidence in the government and in the healthcare system has increased; and they willingly choose to be vaccinated. The regression results suggest that gender, age, health condition, political affiliation, source of information, sense of fairness, socio-economic status, and place of residence are significantly associated with individuals' attitudes toward COVID-19 prevention and control. These findings highlight the importance for the government to design epidemic or pandemic policies based on data and to tailor them toward specific demographics.