High-intensity focused ultrasound ablation combined with immunotherapy for treating liver metastases: A prospective non-randomized trial.

PURPOSE: Given the unique features of the liver, it is necessary to combine immunotherapy with other therapies to improve its efficacy in patients of advanced cancer with liver metastases (LM). High-intensity focused ultrasound (HIFU) ablation is now widely used in clinical practice and can enhanced immune benefits. The study is intended to prospectively evaluate the safety and clinical feasibility of HIFU ablation in combination with systemic immunotherapy for patients with liver metastases. METHODS: The study enrolled 14 patients with LM who received ultrasound-guided HIFU ablation combined with immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (anti-PD-1 agents manufactured in China) at Mianyang Central Hospital. Patients were followed up for adverse events (AEs) during the trial, using the CommonTerminology Criteria for Adverse Events v5.0(CTCAE v5.0) as the standard. Tumour response after treatment was assessed using computerized tomography. RESULTS: The 14 patients (age range, 35-84 years) underwent HIFU ablation at 19 metastatic sites and systemic immunotherapy. The mean lesion volume was 179.9 cm3 (maximum: 733.1 cm3). Median follow-up for this trial was 9 months (range: 3-21) months. The study is clinically feasible and acceptable to patients. CONCLUSION: This prospective study confirmed that HIFU combined with immunotherapy is clinically feasible and safe for treating liver metastases.

[Relationship between serum 25-hydroxyvitamin D and handgrip strength in middle-aged and elderly people in five cities of Western China].

OBJECTIVE: To explore the association between serum 25-hydroxyvitamin D [25(OH)D] and handgrip strength in middle-aged and elderly people in 5 cities of Western China. METHODS: Based on the data of a cross-sectional survey conducted in the 5 cities of Western China from February to July 2023, the relevant demographic characteristics of people were collected by questionnaire, handgrip strength was collected by physical examination, and serum 25(OH)D was detected by HPLC-MS/MS. The association between the serum 25(OH)D and handgrip strength was analyzed using Logistic regression and Chi-square test for between-group comparisons models. RESULTS: The prevalence of 25(OH)D deficiency and insufficiency among the middle-aged and elderly people in the 5 cities of Western China was 52.9% and 34.5%, respectively. The people who were older, female, and sampled in winter had lower serum 25(OH)D levels (P < 0.05). The prevalence of loss of handgrip strength among the middle-aged and elderly people was 25.3%. The prevalence of handgrip strength loss was higher in the aged 65-80 participants with 25(OH)D deficiency (45. 0%) than in those with 25(OH)D insufficiency (32.6%) and 25(OH)D sufficiency (20.6%). The highest prevalence of loss of handgrip strength was found in the aged 75-80 participants with 25(OH)D deficiency (62. 1%), followed by the 25(OH)D insufficient group (11.1%, P < 0.05). The study found that middle-aged and elderly people with 25(OH)D deficiency had a 1.4-fold increased risk of handgrip strength loss compared with those with 25(OH)D sufficiency (OR=2.403, 95%CI: 1.202-4.804, P=0.013). No significant association was found between 25(OH)D insufficiency and handgrip strength status in the middle-aged and elderly people. For every 5 µg/L increase in total serum 25(OH)D, the risk of handgrip strength loss reduced by 13.1% (OR=0.869, 95%CI: 0.768-0.982, P=0.025). For every 5 µg/L increase in serum 25(OH)D2, the risk of handgrip strength loss reduced by 24.1% (OR=0.759, 95%CI: 0.582-0.990, P=0.042). No significant association was found between serum 25(OH)D3 levels and the risk of handgrip strength loss. The risk of handgrip strength loss in middle-aged and elderly people was reduced by 25.2% for each incremental increase in the total serum 25(OH)D levels (deficient, insufficient and sufficient) (OR=0.748, 95%CI: 0.598-0.936, P=0.011). The risk of handgrip loss was reduced by 40.0% for each incremental increase in serum 25(OH)D levels in the aged 65-80 and aged 65-69 participants, and by 80.0% for each incremental increase in 25(OH)D levels in the aged 75-80 parti-cipants. CONCLUSION: Serum total 25(OH)D and 25(OH)D2 levels are associated with handgrip strength status in middle-aged and elderly people in the 5 cities of Western China.

[18F]FDG PET integrated with structural MRI for accurate brain age prediction.

PURPOSE: Brain aging is a complex and heterogeneous process characterized by both structural and functional decline. This study aimed to establish a novel deep learning (DL) method for predicting brain age by utilizing structural and metabolic imaging data. METHODS: The dataset comprised participants from both the Universal Medical Imaging Diagnostic Center (UMIDC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The former recruited 395 normal control (NC) subjects, while the latter included 438 NC subjects, 51 mild cognitive impairment (MCI) subjects, and 56 Alzheimer's disease (AD) subjects. We developed a novel dual-pathway, 3D simple fully convolutional network (Dual-SFCNeXt) to estimate brain age using [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and structural magnetic resonance imaging (sMRI) images of NC subjects as input. Several prevailing DL models were trained and tested using either MRI or PET data for comparison. Model accuracies were evaluated using mean absolute error (MAE) and Pearson's correlation coefficient (r). Brain age gap (BAG), deviations of brain age from chronologic age, was correlated with cognitive assessments in MCI and AD subjects. RESULTS: Both PET- and MRI-based models achieved high prediction accuracy. The leading model was the SFCNeXt (the single-pathway version) for PET (MAE = 2.92, r = 0.96) and MRI (MAE = 3.23, r = 0.95) on all samples. By integrating both PET and MRI images, the Dual-SFCNeXt demonstrated significantly improved accuracy (MAE = 2.37, r = 0.97) compared to all single-modality models. Significantly higher BAG was observed in both the AD (P < 0.0001) and MCI (P < 0.0001) groups compared to the NC group. BAG correlated significantly with Mini-Mental State Examination (MMSE) scores (r=-0.390 for AD, r=-0.436 for MCI) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores (r = 0.333 for AD, r = 0.372 for MCI). CONCLUSION: The integration of [18F]FDG PET with structural MRI enhances the accuracy of brain age prediction, potentially introducing a new avenue for related multimodal brain age prediction studies.

Mechanism of Preventing Recurrence of Stage II-III Colorectal Cancer Metastasis with Immuno-inflammatory and Hypoxic Microenvironment by a Four Ingredients Chinese Herbal Formula: A Bioinformatics and Network Pharmacology Analysis.

BACKGROUND: Colorectal Cancer (CRC) is one of the top three malignancies with the highest incidence and mortality. OBJECTIVE: The study aimed to identify the effect of Traditional Chinese Medicine (TCM) on postoperative patients with stage II-III CRC and explore the core herb combination and its mechanism. METHODS: An observational cohort study was conducted on patients diagnosed with stage II-III CRC from January 2016 to January 2021. The primary outcome was disease-free survival, which was compared between the patients who received TCM or not, and the secondary outcome was the hazard ratio. The relevance principle was used to obtain the candidate herb combinations, and the core combination was evaluated through an assessment of efficacy and representativeness. Then, biological processes and signaling pathways associated with CRC were obtained by Gene Ontology function, Kyoto Encyclopedia of Gene and Genomes pathway, and Wikipathway. Furthermore, hub genes were screened by the Kaplan-Meier estimator, and molecular docking was employed to predict the binding sites of key ingredients to hub genes. The correlation analysis was employed for the correlations between the hub genes and tumor-infiltrating immune cells and hypoxiarelated genes. Ultimately, a quantitative polymerase chain reaction was performed to verify the regulation of hub genes by their major ingredients. RESULTS: A total of 707 patients were included. TCM could decrease the metastatic recurrence associated with stage II-III CRC (HR: 0.61, log-rank P < 0.05). Among those patients in the TCM group, the core combination was Baizhu → Yinchen, Chenpi, and Fuling (C combination), and its antitumor mechanism was most likely related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients, quercetin and tangeretin. The expression of these genes was significantly correlated with both tumor-infiltrating immune cells and hypoxia- related genes. In addition, quercetin and tangeretin down-regulated the mRNA levels of BCL2L1, XIAP, and TOP1, thereby inhibiting the growth of HCT116 cells. CONCLUSION: Overall, a combination of four herbs, Baizhu → Yinchen, Chenpi, and Fuling, could reduce metastatic recurrence in postoperative patients with stage II-III CRC. The mechanism may be related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients quercetin and tangeretin.

Unveiling the Noncovalent Interactions between Formamide and Heteroaromatics: Microwave Spectroscopy of the Formamide Complexes with Furan and Thiophene.

The noncovalent interactions between formamide (FM) and the heteroaromatic compounds (furan and thiophene) were investigated through microwave spectroscopy and theoretical calculations. Each of the investigated complexes exhibits a single rotational spectrum corresponding to the lowest energy structure predicted theoretically. In the detected structures, N-H···O and C-H···O hydrogen bonds dominate the complexation between FM and furan, resulting in a planar configuration. Conversely, a superposed configuration linked by a N-H···π hydrogen bond and C═O···π contact is observed for the FM-thiophene complex. In both cases, hydrogen bonding interactions with N-H as proton donor rank as the dominant forces, and the interaction energy of N-H···O is larger than that of N-H···π. It was found that the electrostatic component is the largest contributor to the attraction between FM and furan, while the dispersion component is the most significant attractive factor in the FM-thiophene complex. These findings highlight the distinct features of hydrogen bonding interactions of amides with heteroaromatics in the studied complexes.

H2B oncohistones cause homologous recombination defect and genomic instability through reducing H2B monoubiquitination in Schizosaccharomyces pombe.

Canonical oncohistones are histone H3 mutations in the N-terminal tail associated with tumors and affect gene expression by altering H3 post-translational modifications (PTMs) and the epigenetic landscape. Noncanonical oncohistone mutations occur in both tails and globular domains of all four core histones and alter gene expression by perturbing chromatin remodeling. However, the effects and mechanisms of noncanonical oncohistones remain largely unknown. Here we characterized 16 noncanonical H2B oncohistones in the fission yeast Schizosaccharomyces pombe. We found that seven of them exhibited temperature sensitivities and 11 exhibited genotoxic sensitivities. A detailed study of two of these onco-mutants H2BG52D and H2BP102L revealed that they were defective in homologous recombination (HR) repair with compromised histone eviction and Rad51 recruitment. Interestingly, their genotoxic sensitivities and HR defects were rescued by the inactivation of the H2BK119 deubiquitination function of Ubp8 in the Spt-Ada-Gcn5-Acetyltransferase (SAGA) complex. The levels of H2BK119 monoubiquitination (H2Bub) in the H2BG52D and H2BP102L mutants are reduced in global genome and at local DNA break sites presumably due to enhanced recruitment of Ubp8 onto nucleosomes and are recovered upon loss of H2B deubiquitination function of the SAGA complex. Moreover, H2BG52D and H2BP102L heterozygotes exhibit genotoxic sensitivities and reduced H2Bub in cis. We therefore conclude that H2BG52D and H2BP102L oncohistones affect HR repair and genome stability via the reduction of H2Bub and propose that other noncanonical oncohistones may also affect histone PTMs to cause diseases.

Characterization of extrachromosomal circular DNAs in plasma of patients with clear cell renal cell carcinoma.

BACKGROUND AND PURPOSE: Extrachromosomal circular DNAs (eccDNAs) have been recognized for their significant involvement in numerous biological processes. Nonetheless, the existence and molecular characteristics of eccDNA in the peripheral blood of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have not yet been reported. Our aim was to identify potentially marked plasma eccDNAs in ccRCC patients. METHODS AND MATERIALS: The detection of plasma eccDNA in ccRCC patients and healthy controls was performed using the Tn5-tagmentation and next-generation sequencing (NGS) method. Comparisons were made between ccRCC patients and healthy controls regarding the distribution of length, gene annotation, pattern of junctional nucleotide motif, and expression pattern of plasma eccDNA. RESULTS: We found 8,568 and 8,150 plasma eccDNAs in ccRCC patients and healthy controls, respectively. There were no statistical differences in the length distribution, gene annotation, and motif signature of plasma eccDNAs between the two groups. A total of 701 differentially expressed plasma eccDNAs were identified, and 25 plasma eccDNAs with potential diagnostic value for ccRCC have been successfully screened. These up-regulated plasma eccDNAs also be indicated to originate from the genomic region of the tumor-associated genes. CONCLUSION: This work demonstrates the characterization of plasma eccDNAs in ccRCC and suggests that the up-regulated plasma eccDNAs could be considered as a promising non-invasive biomarker in ccRCC.

A next-generation BRAF inhibitor overcomes resistance to BRAF inhibition in patients with BRAF-mutant cancers using pharmacokinetics-informed dose escalation.

RAF inhibitors have transformed treatment for BRAF V600-mutant cancer patients, but clinical benefit is limited by adaptive induction of ERK signaling, genetic alterations that induce BRAF V600 dimerization, and poor brain penetration. Next-generation pan-RAF dimer inhibitors are limited by narrow therapeutic index. PF-07799933 (ARRY-440) is a brain-penetrant, selective, pan-mutant BRAF inhibitor. PF-07799933 inhibited signaling in vitro, disrupted endogenous mutant-BRAF:wild-type-CRAF dimers, and spared wild-type ERK signaling. PF-07799933 ± binimetinib inhibited growth of mouse xenograft tumors driven by mutant BRAF that functions as dimers and by BRAF V600E with acquired resistance to current RAF inhibitors. We treated patients with treatment-refractory BRAF-mutant solid tumors in a first-in-human clinical trial (NCT05355701) that utilized a novel, flexible, pharmacokinetics-informed dose escalation design that allowed rapid achievement of PF-07799933 efficacious concentrations. PF-07799933 ± binimetinib was well-tolerated and resulted in multiple confirmed responses, systemically and in the brain, in BRAF-mutant cancer patients refractory to approved RAF inhibitors.

Development and validation of a model for predicting upstage in minimally invasive lung adenocarcinoma in Chinese people.

BACKGROUND: Sublobar resection for ground-glass opacity became a recommend surgery choice supported by the JCOG0804/JCOG0802/JCOG1211 results. Sublobar resection includes segmentectomy and wedge resection, wedge resection is suitable for non-invasive lesions, but in clinical practice, when pathologists are uncertain about the intraoperative frozen diagnosis of invasive lesions, difficulty in choosing the appropriate operation occurs. The purpose of this study was to analyze how to select invasive lesions with clinic-pathological characters. METHODS: A retrospective study was conducted on 134 cases of pulmonary nodules diagnosed with minimally invasive adenocarcinoma by intraoperative freezing examination. The patients were divided into two groups according to intraoperative frozen results: the minimally invasive adenocarcinoma group and the at least minimally invasive adenocarcinoma group. A variety of clinical features were collected. Chi-square tests and multiple regression logistic analysis were used to screen out independent risk factors related to pathological upstage, and then ROC curves were established. In addition, an independent validation set included 1164 cases was collected. RESULTS: Independent risk factors related to pathological upstage were CT value, maximum tumor diameter, and frozen result of AL-MIA. The AUC of diagnostic mode was 71.1% [95%CI: 60.8-81.3%]. The independent validation included 1164 patients, 417 (35.8%) patients had paraffin-based pathology of invasive adenocarcinoma. The AUC of diagnostic mode was 75.7% [95%CI: 72.9-78.4%]. CONCLUSIONS: The intraoperative frozen diagnosis was AL-MIA, maximum tumor diameter larger than 15 mm and CT value is more than - 450Hu, highly suggesting that the lung GGO was invasive adenocarcinoma which represent a higher risk to recurrence. For these patients, sublobectomy would be insufficient, lobectomy or complementary treatment is encouraged.

Research on proactive defense and dynamic repair of complex networks considering cascading effects.

Cascading effects can result in the nonlinear propagation of failures in complex networks, ultimately leading to network collapse. Research on the fault propagation principles, defense strategies, and repair strategies can help mitigate the effects of cascading failures. Especially, proactive defense and dynamic repair are flexible and effective methods to ensure network security. Most studies on the cascade of complex networks are based on the unprocessed initial information of the network. However, marginal nodes are a type of node that cloaks the initial information of the network. In this study, we rank the importance of nodes according to the intensity of network energy confusion after the removal of this node, clarify the meaning of marginal nodes and proposed two methods to screen marginal nodes. The results indicated that the proactive removal of marginal nodes can effectively reduce the effect of cascading failures without causing any negative disturbance to the energy flow of the network. In addition, network repair according to the proposed strategy can minimize the cascade effect in the repair process and improve repair efficiency.

Species' geographical range, environmental range and traits lead to specimen collection preference of dominant plant species of grasslands in Northern China.

Many different factors, such as species traits, socio-economic factors, geographical and environmental factors, can lead to specimen collection preference. This study aims to determine whether grassland specimen collection in China is preferred by species traits (i.e., plant height, flowering and fruiting period), environmental range (i.e., the temperature and precipitation range) and geographical range (i.e., distribution range and altitudinal range). Ordinary least squares models and phylogenetic generalized linear mixed models were used to analyze the relationships between specimen number and the explanatory variables. Random Forest models were then used to find the most parsimonious multivariate model. The results showed that interannual variation in specimen number between 1900 and 2020 was considerable. Specimen number of these species in southeast China was notably lower than that in northwest China. Environmental range and geographical range of species had significant positive correlations with specimen number. In addition, there were relatively weak but significant associations between specimen number and species trait (i.e., plant height and flowering and fruiting period). Random Forest models indicated that distribution range was the most important variable, followed by flowering and fruiting period, and altitudinal range. These findings suggest that future floristic surveys should pay more attention to species with small geographical range, narrow environmental range, short plant height, and short flowering and fruiting period. The correction of specimen collection preference will also make the results of species distribution model, species evolution and other works based on specimen data more accurate.

Infant Formulas With Partially or Extensively Hydrolyzed Milk Proteins for the Prevention of Allergic Diseases: A Systematic Review and Meta-Analysis of Clinical Trials.

Despite the widely recommended usage of partially hydrolyzed formula (PHF) or extensively hydrolyzed formula (EHF) of milk protein for preventing allergic diseases (ADs), clinical studies have been inconclusive regarding their efficacy compared with that of cow's milk formula (CMF) or breast milk (BM). We aimed to systematically evaluate the effects of PHF or EHF compared with those of CMF or BM on risk of ADs (cow's milk allergy, allergic rhinitis, eczema, asthma, wheeze, food allergy, and sensitization) in children. We searched PubMed, Embase, Cochrane Library, and Web of Science for clinical trials published from inception to 21 October, 2022. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to grade the strength of evidence. Overall, 24 trials (10,950 infants) were included, 17 of which specifically included high-risk infants. GRADE was low for the evidence that, compared with CMF, infants early fed with EHF had lower risk of cow's milk allergy at age 0-2 y [relative risk (RR): 0.62; 95% CI: 0.39, 0.99]. Moderate evidence supported that PHF and EHF reduced risk of eczema in children aged younger or older than 2 y, respectively (RR: 0.71; 95% CI: 0.52, 0.96; and RR: 0.79; 95% CI: 0.67, 0.94, respectively). We also identified moderate systematic evidence indicating that PHF reduced risk of wheeze at age 0-2 y compared with CMF (RR: 0.50; 95% CI: 0.29, 0.85), but PHF and EHF increased the risk compared with BM (RR: 1.61; 95% CI: 1.11, 2.31; and RR: 1.64; 95% CI: 1.26, 2.14). Neither PHF nor EHF had significant effects on other ADs in children of any age. In conclusion, compared with CMF, PHF, or EHF had different preventive effect on cow's milk allergy, eczema, and wheeze. Compared with BM, both PHF and EHF may increase risk of wheeze but not other ADs. Given that most trials included only high-risk infants, more research on non-high-risk infants is warranted before any generalization is attempted. This protocol was registered at PROSPERO as CRD42022320787.

La-Doped Sm2Zr2O7/PU-Coated Leather Composites with Enhanced Mechanical Properties and Highly Efficient Photocatalytic Performance.

Flexible La-doped Sm2Zr2O7/polyurethane (PU) coated leather composites were synthesized using a one-step hydrothermal method, with highly efficient photocatalytic degradation properties by coating the La-doped Sm2Zr2O7/PU emulsion onto the leather and drying it. The phase composition and optical properties of the as-prepared photocatalytic material were systematically characterized. The result revealed that La was doped in Sm2Zr2O7 successfully, and the prepared samples still possessed pyrochlore structure. The absorption edge of the prepared samples exhibited a red-shift with the increase in La doping, indicating that La doping could broaden the absorbance range of the La-doped Sm2Zr2O7 materials. The catalytic performance of La-doped Sm2Zr2O7/PU composite emulsion coating on the photocatalytic performance of leather was studied with Congo red solution as the target pollutant. The results showed that the best photocatalytic property was found in the 5% La-doped Sm2Zr2O7 nanomaterial at a concentration of 3 g/L. The resulting 5% La-doped Sm2Zr2O7 nanomaterial exhibited a high specific surface area of 73.5 m2/g. After 40 min of irradiation by a 450 W xenon lamp, the degradation rate of Congo red reached 93%. Moreover, after surface coating, the La-doped Sm2Zr2O7/PU coated leather composites showed obviously improved mechanical properties, as the tensile strength of La-doped Sm2Zr2O7/PU coated leather composites increased from 6.3 to 8.4 MPa. The as-prepared La-doped Sm2Zr2O7/PU coated leather composites with enhanced mechanical properties and highly efficient photocatalytic performance hold promising applications in the treatment of indoor volatile organic compounds.

Preparation of a novel antibacterial magnesium carbonate coating on a titanium surface and its in vitro biocompatibility.

Magnesium-based coatings have attracted great attention in surface modification of titanium implants due to their superior angiogenic and osteogenic properties. However, their biological effects as a carbonate-based constituent remain unrevealed. In this study, magnesium carbonate coatings were prepared on titanium surfaces under hydrothermal conditions and subsequently treated with hydrogen peroxide. Also, their antibacterial activity and in vitro cell biocompatibility were evaluated. The obtained coatings consisted of nanoparticles without cracks and exhibited excellent adhesion to the substrate. X-ray diffraction (XRD) results indicated pure magnesium carbonate coatings formed on the Ti surface after hydrothermal treatment. After hydrogen peroxide treatment, the phase composition of the coatings had no obvious change. Compared to the untreated coatings, the hydrogen peroxide-treated coatings showed increased surface roughness and hydrophilicity. Co-culture with Staphylococcus aureus (S. aureus) demonstrated that the obtained coatings had good antibacterial activity. In vitro cell culture results showed that the hydrogen peroxide-treated coatings enhanced the viability, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). These findings suggest that this MgCO3-based coating exhibits excellent antibacterial performance and osteogenic potential. Based on the above, this study provides a simple method for preparing titanium implants with dual antibacterial and osteogenic capabilities, holding great promise in clinical applications.

Bifidobacterium bifidum supplementation improves ischemic stroke outcomes in elderly patients: A retrospective study.

This retrospective study aimed to explore the therapeutic potential of Bifidobacterium bifidum supplementation on elderly ischemic stroke patients. We retrospectively analyzed electronic medical records from 153 elderly ischemic stroke patients. Patients were stratified into 2 groups: those receiving B bifidum supplementation (Intervention group, n = 73) and those receiving standard treatment without any additional supplementation (Control group, n = 80). Outcomes were assessed using the National Institutes of Health Stroke Scale (NIHSS), Montreal Cognitive Assessment (MoCA), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS). Inflammatory markers, immunological indicators, neurotrophic factor, and gut-brain axis (GBA)-related markers were also evaluated at baseline and during 4-week follow-up. Compared to the control group, the intervention group exhibited significant improvements in the NIHSS, MoCA, SDS and SAS scores (P < .001). Enhanced levels of brain-derived neurotrophic factor (BDNF) and reduced levels of NPY were observed in the intervention group. Additionally, inflammatory markers, including IL-6, IL-8, IL-1ß, and TNF-α, were significantly reduced in the intervention group, as well as significant increases in immunoglobulin levels (Ig A, Ig G, and Ig M) (P < .001). Besides, lower incidences of diarrhea and constipation were observed in the intervention group (P < .001), while the incidence of abdominal pain was no significant changed. B bifidum supplementation offers promising therapeutic benefits in improving neurological, cognitive, and psychological outcomes in elderly ischemic stroke patients, which may be achieved by regulating the GBA, reducing inflammation and promoting immune function. These findings highlight the importance of integrating gut health strategies in stroke management.

The Schizosaccharomyces pombe DEAD-box protein Mss116 is required for mitoribosome assembly and mitochondrial translation.

DEAD-box helicases are important players in mitochondrial gene expression, which is necessary for mitochondrial respiration. In this study, we characterized Schizosaccharomyces pombe Mss116 (spMss116), a member of the family of DEAD-box RNA helicases. Deletion of spmss116 in a mitochondrial intron-containing background significantly reduced the levels of mitochondrial DNA (mtDNA)-encoded cox1 and cob1 mRNAs and impaired mitochondrial translation, leading to a severe respiratory defect and a loss of cell viability during stationary phase. Deletion of mitochondrial introns restored the levels of cox1 and cob1 mRNAs to wide-type (WT) levels but could not restore mitochondrial translation and respiration in Δspmss116 cells. Furthermore, deletion of spmss116 in both mitochondrial intron-containing and intronless backgrounds impaired mitoribosome assembly and destabilization of mitoribosomal proteins. Our findings suggest that defective mitochondrial translation caused by deletion of spmss116 is most likely due to impaired mitoribosome assembly.

Unveiling the underappreciated: The bonding features of C-H⋯S-S interactions observed from rotational spectroscopy.

The C-H⋯S-S interactions are fundamentally important to understand the stability of biomacromolecules and their binding with small molecules, but they are still underappreciated. Herein, we characterized the C-H⋯S-S interactions in model molecular complexes. The rotational spectra of the complexes of diethyl disulfide with CH2CH2 and CH2CHF were measured and analyzed. All the detected structures are mainly stabilized by a C-H⋯S-S hydrogen bond, providing stabilization energies of 2.3-7.2 kJ mol-1. Incidental C-H⋯π or C-H⋯F interactions enhance the stabilization of the complexes. London dispersion, which accounts for 54%-68% of the total attractions, is the main driving force of stabilization. The provided bonding features of C-H⋯S-S are crucial for understanding the stabilizing role of this type of interaction in diverse processes such as supramolecular recognition, protein stability, and enzyme activity.

AßPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease.

As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AßPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AßPP/PS1 mice. Phosphorylated tau (p-tau) mediates AßPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AßPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.

Ultrafine Ni-MoOx Nanoparticles Anchored on Nitrogen-Doped Carbon Nanosheets: A Highly Efficient Noble-Metal-Free Catalyst for Ammonia Borane Hydrolysis.

The development of low-cost and high-efficiency catalysts for the hydrolytic dehydrogenation of ammonia borane (AB, NH3BH3) is still a challenging technology. Herein, ultrafine MoOx-doped Ni nanoparticles (~3.0 nm) were anchored on g-C3N4@glucose-derived nitrogen-doped carbon nanosheets via a phosphate-mediated method. The strong adsorption of phosphate-mediated nitrogen-doped carbon nanosheets (PNCS) for metal ions is a key factor for the preparation of ultrasmall Ni nanoparticles (NPs). Notably, the alkaline environment formed by the reduction of metal ions removes the phosphate from the PNCS surface to generate P-free (P)NCS so that the phosphate does not participate in the subsequent catalytic reaction. The synthesized Ni-MoOx/(P)NCS catalysts exhibited outstanding catalytic properties for the hydrolysis of AB, with a high turnover frequency (TOF) value of up to 85.7 min-1, comparable to the most efficient noble-metal-free catalysts and commercial Pt/C catalyst ever reported for catalytic hydrogen production from AB hydrolysis. The superior performance of Ni-MoOx/(P)NCS can be ascribed to its well-dispersed ultrafine metal NPs, abundant surface basic sites, and electron-rich nickel species induced by strong electronic interactions between Ni-MoOx and (P)NCS. The strategy of combining multiple modification measures adopted in this study provides new insights into the development of economical and high-efficiency noble-metal-free catalysts for energy catalysis applications.