In Situ Hydroxide Growth over Nickel-Iron Phosphide with Enhanced Overall Water Splitting Performances.

In this work, three dimensional (3D) self-supported Ni-FeOH@Ni-FeP needle arrays with core-shell heterojunction structure are fabricated via in situ hydroxide growth over Ni-FeP surface. The as-prepared electrodes show an outstanding oxygen evolution reaction (OER) performance, only requiring the low overpotential of 232 mV to reach 200 mA cm-2 with the Tafel slop of 40 mV dec-1. For overall water splitting, an alkaline electrolyzer with these electrodes only requires a cell voltage of 2.14 V to reach 1 A cm-2. Mechanistic investigations for such excellent electrocatalytic performances are utilized by in situ Raman spectroscopy in conjunction with density functional theory (DFT) calculations. The computation results present that Ni-FeOH@Ni-FeP attains better intrinsic conductivity and the D-band center (close to that of the ideal catalyst), thus giving superior excellent catalytic performances. Likewise, the surface Ni-FeOH layer can improve the structural stability of Ni-FeP cores and attenuate the eventual formation of irreversible FeOOH products. More importantly, the appearance of FeOOH intermediates can effectively decrease the energy barrier of NiOOH intermediates, and then rapidly accelerate the sluggish reaction dynamics, as well as further enhance the electrocatalytic activities, reversibility and cycling stability.

Long-term associations of PM1 versus PM2.5 and PM10 with asthma and asthma-related respiratory symptoms in the middle-aged and elderly population.

Background: Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods: We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results: We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02-1.45); PM2.5: 1.24 (1.04-1.48); PM10: 1.30 (1.07-1.57)), wheeze (PM1: 1.27 (1.11-1.44); PM2.5: 1.30 (1.14-1.48); PM10: 1.34 (1.17-1.55)), persistent cough (PM1: 1.33 (1.06-1.66); PM2.5: 1.36 (1.09-1.71); PM10: 1.31 (1.02-1.68)) and dyspnoea (PM1: 2.10 (1.84-2.41); PM2.5: 2.17 (1.90-2.48); PM10: 2.29 (1.96-2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion: Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

Association of NLRP3 and IL-4 VNTR polymorphisms and genetic susceptibility to preeclampsia: A case-control study.

INTRODUCTION: Abnormalities in the maternal immune system and insufficient gestational immune tolerance may significantly contribute to the development of preeclampsia (PE). The NLR family pyrin domain containing 3 (NLRP3) functions as a pattern recognition receptor that identifies pathogen-associated molecular patterns. Interleukin-4 (IL-4) is a potent anti-inflammatory cytokine that modulates the immune response. Therefore, this study aims to elucidate the impact of NLRP3 and IL-4 variable number of tandem repeats (VNTR) polymorphisms on susceptibility to PE. MATERIALS AND METHODS: A total of 1,018 patients with PE and 1,007 normal pregnant women were recruited as the case group and the control group, respectively. Peripheral blood DNA was extracted, and NLRP3 and IL-4 VNTR polymorphisms were genotyped using polymerase chain reaction and gel electrophoresis. Genotypes and allele frequencies of pregnant women were assessed in both cohorts. RESULTS: The NLRP3 VNTR 9-7 genotype in the PE group was significantly lower than that in the control group, but 9 and 14 allele frequencies were significantly higher in patients with PE. Individuals with IL-4 VNTR genotypes 1-2 had a lower risk of PE than controls, and the IL-4 VNTR 2 allele frequency was significantly lower in patients with PE. CONCLUSIONS: This study, the first of its kind in the literature, evaluates the impact of NLRP3 VNTR and IL-4 VNTR polymorphisms on PE, revealing a significant correlation with PE susceptibility. This investigation contributes to understanding the pathogenesis of PE and provides a reference point for developing strategies to prevent and treat the disease in the future.

Nab-paclitaxel plus S-1 versus nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer: a multicenter, randomized, phase II study.

BACKGROUND: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). METHODS: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. CONCLUSION: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).

Hybrid argon plasma coagulation for the treatment of Barrett's esophagus: A prospective, multicenter study.

BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.

Fc-enhanced anti-CTLA-4, anti-PD-1, doxorubicin, and ultrasound-mediated BBB opening: A novel combinatorial immunotherapy regimen for gliomas.

BACKGROUND: Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in "cold" and immunotherapy-refractory cancers. METHOD: We evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor associated macrophages/microglia (TAMs). RESULTS: FcE-aCTLA-4 demonstrated high-affinity binding to FcγRIV, the mouse ortholog of human FcγRIIIA, which was highly expressed in TAMs in human glioblastoma, most robustly at diagnosis. Notably, FcE-aCTLA-4 mediated selective depletion of intra-tumoral regulatory T cells (Tregs) via TAM-mediated phagocytosis, while sparing peripheral Tregs. Doxorubicin, a chemotherapeutic drug with immunomodulatory functions, was found to upregulate FcγRIIIA on TAMs in glioblastoma patients who received doxorubicin and anti-PD-1 with concomitant LIPU/MB. In murine models of immunotherapy-resistant gliomas, a combinatorial regimen of FcE-aCTLA-4, anti-PD-1, and doxorubicin with LIPU/MB, achieved a 90% cure rate, that was associated robust infiltration of activated CD8+ T cells and establishment of immunological memory as evidenced by rejection upon tumor rechallenge. CONCLUSION: Our findings demonstrate that FcE-aCTLA-4 promotes robust immunomodulatory and anti-tumor effects in murine gliomas and is significantly enhanced when combined with anti-PD-1, doxorubicin, and LIPU/MB. We are currently investigating this combinatory strategy in a clinical trial (clinicaltrials.gov NCT05864534).

Safety and effectiveness of using Disposable Ultrasonic shears to coagulate 5-7 mm blood vessels: protocol for a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial.

BACKGROUND: The ultrasonic scalpel is widely used during surgery. It is safe and effective to close the pulmonary artery branch vessels of 7 mm or below with an ultrasonic energy device as reported. However, there have been no multicenter randomized clinical trial to assess the safety and effectiveness of using ultrasonic scalpel to coagulate 5-7 mm blood vessels in thoracic surgery. METHODS: This is a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial. A total of 144 eligible patients planning to undergo lung or esophageal surgery will be randomly allocated to the experimental group and the control group. The investigational product (Disposable Ultrasonic Shears manufactured by Reach Surgical, Inc.) and the control product (Harmonic Ace + 7, 5 mm Diameter Shears with Advanced Hemostasis) will be used in each group. The primary endpoint is the success rate of coagulating target blood vessels during surgery. Secondary endpoints include postoperative rebleeding, intraoperative bleeding volume, drainage volume, surgical duration, etc. Postoperative follow-up before and after discharge will be performed. DISCUSSION: This clinical trial aims to evaluate the safety and effectiveness of using the investigational product (Disposable Ultrasonic Shears manufactured by Reach Surgical, Inc.) and that of the control product (Harmonic Ace + 7, 5 mm Diameter Shears with Advanced Hemostasis) to coagulate 5-7 mm blood vessels in thoracic surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06002737. The trial was prospectively registered on 16 August 2023, https://www. CLINICALTRIALS: gov/study/NCT06002737 .

Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

MOF-Derived Zn/N-Doped Porous Carbon Film on a Carbon Nanotube for High-Performance Supercapacitors.

Designing high-performance binder-free electrochemical electrodes is crucially important toward supercapacitors. In this paper, a Zn/N-doped porous carbon film coating on flexible carbon nanotubes (ZIF-8@CT-800) derived from the epitaxial Zn-MOF film growth on cotton textile was successfully fabricated via a combination of the liquid-phase epitaxial (LPE) method and calcination treatments. The ZIF-8@CT-800 serves directly as a self-supported electrode for supercapacitors and exhibits a high areal capacitance of 930 mF·cm-2 at a current density of 1 mA·cm-2 and a good recyclability of 86% after 2000 cycles. The excellent supercapacitor property is ascribed to the unique structural design of ZIF-8@CT-800, which provides appropriate channels for enhanced electronic and ionic transport as well as increased surface area for accessing more electrolyte ions. This work will provide significant guidance for designing MOF-derived porous carbon to construct flexible binder-free electrode materials with high electrochemical performance.

Subminimum Inhibitory Concentrations Tetracycline Antibiotics Induce Biofilm Formation in Minocycline-Resistant Klebsiella pneumonia by Affecting Bacterial Physical and Chemical Properties and Associated Genes Expression.

Biofilm formation of Klebsiella pneumoniae can protect bacteria from antibiotics and is difficult to eradicate. Thus, the influence of subinhibitory concentrations of antibiotics on bacteria is becoming increasingly important. Our study showed that subminimum inhibitory concentrations (sub-MICs) of tetracycline antibiotics can increase biofilm formation in minocycline-resistant Klebsiella pneumoniae clinical strains. However, in the bacterial adhesion and invasion experiments, the adhesion and invasion ability decreased and the survival rate of Galleria mellonella increased. Under sub-MICs of tetracycline antibiotics treatment, abnormal stretching of bacteria was observed by scanning electron microscopy. Treatment with sub-MICs of tetracyclines leads to increased surface hydrophobicity and eDNA content and decreased outer membrane permeability. The expression levels of the fimA, luxS, qseB, and qseC genes decreased, the expression level of mrkA increased, and the expression level of acrA was inconsistent under different tetracycline antibiotics treatments. Together, our results suggested that the increase in Klebsiella pneumoniae biofilm formation caused by sub-MICs of tetracycline antibiotics may occur by affecting bacterial physical and chemical properties and associated genes expression.

Analysis of the improved mechanism of Rhodobacter sphaeroides VK-2-3 coenzyme Q10 by reverse metabolic engineering.

Coenzyme Q10 (CoQ10) is an essential medicinal ingredient. In this study, we obtained a high-yielding mutant strain of CoQ10, VK-2-3, by subjecting R. sphaeroides V-0 (V-0) to a 12C6+ heavy ion beam and high-voltage prick electric field treatment. To investigate the mutation mechanism, the complete genomes of VK-2-3 and V-0 were sequenced. Collinearity analysis revealed that the nicotinamide adenine dinucleotide-dependent dehydrogenase (NAD) gene underwent rearrangement in the VK-2-3 genome. The NAD gene was overexpressed and silenced in V-0, and this construct was named RS.NAD and RS.ΔNAD. The results showed that the titers of CoQ10 in the RS.NAD and RS.ΔNAD increased and decreased by 16.00 and 33.92%, respectively, compared to those in V-0, and these differences were significant. Our results revealed the mechanism by which the VK-2-3 CoQ10 yield increases through reverse metabolic engineering, providing insights for genetic breeding and mechanistic analysis.

Computerized cognitive remediation therapy on cognitive impairment and social function in patients with chronic schizophrenia.

BACKGROUND: Patients with schizophrenia may have various disease manifestations, most of which gradually tend toward incurable chronic decline, leading to mental disability. The basic symptoms of the disease can impair social function, whereas long-term hospitalization produces hospitalization syndrome, causing serious damage to social function. AIM: To investigate the effects of Computerized Cognitive Remediation Therapy (CCRT) on cognitive and social functioning in patients with chronic schizophrenia. METHODS: A retrospective analysis of 120 patients with chronic schizophrenia in Shanghai Pudong New Area Mental Health Center was performed. They were divided into an intervention group (60 cases treated with CCRT combined with conventional medication) and a control group (60 cases treated with conventional medication). After treatment, effects on cognitive function and social roles were observed in both groups. The Positive and Negative Syndrome Scale (PANSS) was used to assess the patients' psychiatric symptoms. The Wisconsin Card Sorting Test (WCST) was used to assess the patients' cognitive functioning, and the Social Functioning Scale for Psychiatric Inpatients (SSPI) was used to assess the social functioning of the inpatient psychiatric patients. RESULTS: No significant differences were observed in the PANSS, WCST, and SSPI intergroup scores before treatment (P > 0.05). After 2, 4, and 6 wk of therapy, general psychopathological factors, positive symptoms, negative symptoms, and total PANSS scores of PANSS in the intervention group were lower than in the control group (P < 0.05). After 2, 4, and 6 wk of treatment, the number of false responses, number of persistent bugs, and total responses in the WCST were significantly lower in the intervention group than in the control group (P < 0.05), and the amount of completed classification was significantly higher than in the control group (P < 0.05). After 2, 4, and 6 wk of therapy, the SSPI scores were significantly greater than those of the controls (P < 0.05). After 6 wk of treatment, the efficacy rates of the control and intervention groups were 81.67% and 91.67%, respectively. The curative effect in the intervention group was significantly higher than that in the control group (P < 0.05). CONCLUSION: CCRT can significantly improve cognitive function and social abilities in patients with chronic schizophrenia.

Predicting Cd(II) adsorption capacity of biochar materials using typical machine learning models for effective remediation of aquatic environments.

The screening and design of "green" biochar materials with high adsorption capacity play a pivotal role in promoting the sustainable treatment of Cd(II)-containing wastewater. In this study, six typical machine learning (ML) models, namely Linear Regression, Random Forest, Gradient Boosting Decision Tree, CatBoost, K-Nearest Neighbors, and Backpropagation Neural Network, were employed to accurately predict the adsorption capacity of Cd(II) onto biochars. A large dataset with 1051 data points was generated using 21 input variables obtained from batch adsorption experiments, including preparation conditions for biochar (2 features), physical properties of biochar (4 features), chemical composition of biochar (9 features), and adsorption experiment conditions (6 features). The rigorous evaluation and comparison of the ML models revealed that the CatBoost model exhibited the highest test R2 value (0.971) and the lowest RMSE (20.54 mg/g), significantly outperforming all other models. The feature importance analysis using Shapley Additive Explanations (SHAP) indicated that biochar chemical compositions had the greatest impact on model predictions of adsorption capacity (42.2 %), followed by adsorption conditions (37.57 %), biochar physical characteristics (12.38 %), and preparation conditions (7.85 %). The optimal experimental conditions optimized by partial dependence plots (PDP) are as follows: as high Cd(II) concentration as possible, C(%) of 33 %, N(%) of 0.3 %, adsorption time of 600 min, pyrolysis time of 50 min, biochar dosage of less than 2 g/L, O(%) of 42 %, biochar pH value of 11.2, and DBE of 1.15. This study unveils novel insights into the adsorption of Cd(II) and provides a comprehensive reference for the sustainable engineering of biochars in Cd(II) wastewater treatment.

Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer.

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Background and Objectives: Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. Methods: We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Results: Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. Discussion: SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

Seabuckthorn (Hippophae rhamnoides L.) plantation degradation aggravates microbial metabolic C and P limitations on the Northern Loess Plateau in China.

Vegetation degradation in arid and semi-arid regions reduces plant C inputs to the soil, which can impede soil nutrient cycling because of the limited C source for microbial metabolism. However, whether vegetation degradation aggravates microbial nutrient limitation in degraded ecosystems in arid and semi-arid regions is not fully understood. Here, we investigated changes in soil enzyme activity and microbial nutrient limitation along a well-documented gradient of degraded seabuckthorn (Hippophae rhamnoides L.) (slightly degraded, canopy dieback <25 %, moderately degraded, canopy dieback 25 %-75 %, and severely degraded, canopy dieback >75 %) in Liang (long ridge) and gully channel locations in the Pisha Sandstone region of the Loess Plateau, China. We found that as the magnitude of seabuckthorn degradation increased, activities of C-acquiring enzymes and ratios of C:N and C:P enzymes (0.54-0.80 and 0.52-0.77, respectively) increased whereas the N:P enzyme ratio (0.93-0.99) decreased. Stoichiometric modelling further indicated that microorganisms were limited by soil C and P (vector angle >45°) in the seabuckthorn plantation region, and the degradation of seabuckthorn plantation aggravated microbial C and P limitations. Partial least squares path modelling revealed that seabuckthorn degradation (canopy dieback) was the main factor explaining microbial C limitation variations, while soil physicochemical properties (pH and soil moisture content) and understory plant parameters (litter biomass) were the major factors underlying microbial P limitation of long ridge and gully channel formations, respectively. Our findings highlight synergistic changes between aboveground and belowground processes, suggesting an unexpected negative effect of vegetation degradation on soil microbial community and nutrient cycling. These insights offer a direction for the development of plantation nutrients management strategies in semi-arid and arid areas.

Alternative splicing of lncRNA LAIR fine-tunes the regulation of neighboring yield-related gene LRK1 expression in rice.

The diversity in alternative splicing of long noncoding RNAs (lncRNAs) poses a challenge for functional annotation of lncRNAs. Moreover, little is known on the effects of alternatively spliced lncRNAs on crop yield. In this study, we cloned nine isoforms resulting from the alternative splicing of the lncRNA LAIR in rice. The LAIR isoforms are generated via alternative 5'/3' splice sites and different combinations of specific introns. All LAIR isoforms activate the expression of the neighboring LRK1 gene and enhance yield-related rice traits. In addition, there are slight differences in the binding ability of LAIR isoforms to the epigenetic modification-related proteins OsMOF and OsWDR5, which affect the enrichment of H4K16ac and H3K4me3 at the LRK1 locus, and consequently fine-tune the regulation of LRK1 expression and yield-related traits. These differences in binding may be caused by polymorphic changes to the RNA secondary structure resulting from alternative splicing. It was also observed that the composition of LAIR isoforms was sensitive to abiotic stress. These findings suggest that the alternative splicing of LAIR leads to the formation of a functional transcript population that precisely regulates yield-related gene expression, which may be relevant for phenotypic polymorphism-based crop breeding under changing environmental conditions.

Hazard profiles, distribution trends, and sources tracing of rare earth elements in dust of kindergartens in Beijing.

Children, the most vulnerable group in urban populations, are susceptible to the effects of pollution in urban environments. It is significant to evaluate the influence of rare earth elements (REEs) from kindergartens dust (KD) in Beijing on children's health. This study collected surface dust from 73 kindergartens in 16 districts of the mega-city of Beijing, and the concentrations of 14 REEs in KD, including La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu, were detected. The contamination levels, source apportionment, and health exposure risk of REEs were comprehensively investigated. The results indicate that the contamination levels of 14 REEs are within the acceptable range. Nevertheless, Eu, Ce, La, Pr, Nd, Gd, and Sm show high enrichment due to anthropogenic influence. Besides, KD is rich in light rare earth elements (LREEs) (90.97 mg kg-1) compared to heavy rare earth elements (HREEs) (8.65 mg kg-1). The distribution parameter patterns of REEs suggest that complicated anthropogenic sources influence the enrichment of REEs in KD. The main sources of REEs in KD include natural sources (40.64%), mixed high-tech industries and construction (33.89%), and mixed coal-fired, historical industrial, and transportation sources (26.47%). The primary pathway for daily intake of REEs in children is through ingestion, which presents a low but not negligible health risk. This study provides guidance for the effective risk management of REEs in KD.

Modular Synthesis of Polysubstituted α-Phosphorylated Arenes via the Catellani Strategy.

In this paper, we described a palladium/norbornene-catalyzed ortho-C-H phosphormethylation of aryl iodides using XCH2P(O)RR', offering a reliable method for the modular synthesis of polysubstituted α-phosphorylated arenes. Alkenylation, hydrogenation, cyanation, methylation, and arylation were all viable termination steps compatible with the reaction. This method demonstrates excellent functional group tolerance and can be extended to the late-stage modification of bioactive molecules. Furthermore, the synthetic transformations of the products demonstrate the practical utility of this reaction.

STING agonist 8803 reprograms the immune microenvironment and increases survival in preclinical models of glioblastoma.

STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and the Ivy Glioblastoma Atlas, STING expression was found in myeloid populations and in the perivascular space. The STING agonist 8803 increased median survival in multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% of mice were cured. Ex vivo flow cytometry profiling during the therapeutic window demonstrated increases in myeloid tumor trafficking and activation, alongside enhancement of CD8+ T cell and NK effector responses. Treatment with 8803 reprogrammed microglia to express costimulatory CD80/CD86 and iNOS, while decreasing immunosuppressive CD206 and arginase. In humanized mice, where tumor cell STING is epigenetically silenced, 8803 therapeutic activity was maintained, further attesting to myeloid dependency and reprogramming. Although the combination with a STAT3 inhibitor did not further enhance STING agonist activity, the addition of anti-PD-1 antibodies to 8803 treatment enhanced survival in an immune checkpoint blockade-responsive glioma model. In summary, 8803 as a monotherapy demonstrates marked in vivo therapeutic activity, meriting consideration for clinical translation.