Cytological Effects of Cadmium Poisoning and the Protective Effect of Quercetin: A Mechanism Exploration based on the Testicular Lamina Propria.

This comprehensive study delved into the detrimental effects of cadmium (Cd), a toxic heavy metal, on the testicular lamina propria (LP), a key player in spermatogenesis, and the maintenance of testicular stem cell niches. Utilizing transmission electron microscopy, immunohistochemistry, and double-labeling immunofluorescence, the research characterized the structural and cellular components of mouse testicular LP under Cd exposure and investigated the protective effects of quercetin. The findings illustrated that Cd exposure results in significant morphological and cellular modifications within the LP, including the apoptosis of peritubular myoid cells, an upsurge in CD34+ stromal cells displaying anti-apoptotic behaviors, and an excessive production of collagen Type I fibers and extracellular matrix. Remarkably, quercetin effectively counteracted these adverse changes by reversing apoptosis, reducing the proliferation of CD34+ stromal cells, and addressing fibrosis markers, thereby mitigating the cellular damage induced by Cd. This study not only highlighted the critical impact of apoptosis and fibrosis in Cd-related testicular damage but also elucidated the protective mechanism of quercetin, laying the groundwork for future clinical applications in addressing testicular damage from heavy metal poisoning through cellular therapeutics and pharmacological interventions.

Comparative study of pathogen detection methods for central nervous system infections: laboratory testing of tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is a severe central nervous system (CNS) infection with a challenging diagnosis due to inadequate detection methods. This study evaluated current clinical detection methods and their applicability. METHODS: A cohort of 514 CNS infection patients from 2018 to 2020 was studied. Data on general demographics, Cerebrospinal Fluid (CSF) analysis, epidemiology, and clinical outcomes were collected. TBM patients were identified, and the sensitivities of mmetagenomic next-generation sequencing (NGS), GeneXpert, and microbial culture were compared. Kappa statistic assessed the consistency between methods. RESULTS: Among the patients involved, TBM (29%) and neurosyphilis (25%) were the two most prevalent CNS infections. CSF analysis indicated that 76% of patients had leukocytosis, suggesting a potential CNS inflammation. In TBM cases, 92.5% had elevated CSF protein and leukocyte counts. Moreover, the percentage of positive mNGS results was 55.6%. GeneXpert and MTB cultures alone had lower sensitivity, but combined use resulted in a 53.4% positive rate. CONCLUSIONS: This study highlights the high sensitivity of mNGS, comparable to GeneXpert and MTB culture. The combined methods are cost-effective and straightforward, and can partially substitute for mNGS, offering valuable alternatives for TBM diagnosis and providing insights into multiple diagnostic strategies in clinical practice.

Efficacy of PD-1/PD-L1 blockade immunotherapy in recurrent/metastatic high-grade neuroendocrine carcinoma of the cervix: A retrospective study.

Although high-grade neuroendocrine carcinoma of the cervix (HGNECC) accounts for less than 1 % of all cervical cancers, it exhibits marked aggressiveness and resistance to radiation and chemotherapy. We retrospectively investigated the efficacy of immunotherapy for recurrent/metastatic HGNECC in a real-world setting. From September 2016 to December 2022, a total of 29 patients with HGNECC accepted PD-1/PD-L1 inhibitors; of these, six cases (20.7 %) were PD-L1 positive (combined positive score ≥1). According to their primary treatment, the patients were assigned to either a surgery group (n = 14) or a non-surgery group (n = 15). In the surgery group, four patients received anti-PD-1 therapy immediately after surgery, while six, two, one, and one patients started immunotherapy after the first, second, third, and forth recurrence, respectively. In the non-surgery group, seven patients started immunotherapy as part of their primary treatment, while the other four, two, and two patients received anti-PD-1 drugs as the second, third, and forth lines of treatment, respectively. The seven-patient group showed longer progression-free survival after immunotherapy (PFSi) and overall survival than those of their counterparts (P = 0.085 and 0.08, respectively), while this benefit was not observed in other subgroups. No significant correlation was observed between PD-L1 and PFSi expression. Interestingly, one patient with a high tumor mutation burden (TMB-H) had a long PFSi of 26 months and experienced no recurrence until the last follow-up. Based on these findings, we propose that PD-1/PD-L1 inhibitors may prolong the survival of patients with HGNECC who start immunotherapy as the first-line of treatment. This indicates that early immunotherapy may be a better choice for this challenging malignancy. Moreover, the predictive role of TMB-H in immunotherapeutic outcomes requires further investigation.

ProT-Diff: A Modularized and Efficient Strategy for De Novo Generation of Antimicrobial Peptide Sequences by Integrating Protein Language and Diffusion Models.

Antimicrobial peptides (AMPs) are a promising solution for treating antibiotic-resistant pathogens. However, efficient generation of diverse AMPs without prior knowledge of peptide structures or sequence alignments remains a challenge. Here, ProT-Diff is introduced, a modularized deep generative approach that combines a pretrained protein language model with a diffusion model for the de novo generation of AMPs sequences. ProT-Diff generates thousands of AMPs with diverse lengths and structures within a few hours. After silico physicochemical screening, 45 peptides are selected for experimental validation. Forty-four peptides showed antimicrobial activity against both gram-positive or gram-negative bacteria. Among broad-spectrum peptides, AMP_2 exhibited potent antimicrobial activity, low hemolysis, and minimal cytotoxicity. An in vivo assessment demonstrated its effectiveness against a drug-resistant E. coli strain in acute peritonitis. This study not only introduces a viable and user-friendly strategy for de novo generation of antimicrobial peptides, but also provides potential antimicrobial drug candidates with excellent activity. It is believed that this study will facilitate the development of other peptide-based drug candidates in the future, as well as proteins with tailored characteristics.

Differences in cervical sagittal parameters and muscular function among subjects with different cervical spine alignments: a surface electromyography-based cross-sectional study.

Background: We analyzed cervical sagittal parameters and muscular function in different cervical kyphosis types. Methods: This cross-sectional study enrolled subjects with cervical spine lordosis (cervical curvature < -4°) or degenerative cervical kyphosis (cervical curvature > 4°), including C-, S-, and R-type kyphosis. We recorded patients' general information (gender, age, body mass index), visual analog scale (VAS) scores, and the Neck Disability Index (NDI). Cervical sagittal parameters including C2-C7 Cobb angle (Cobb), T1 slope (T1S), C2-C7 sagittal vertical axis (SVA), spino-cranial angle (SCA), range of motion (ROM), and muscular function (flexion-relaxation ratio (FRR) and co-contraction ratio (CCR) of neck/shoulder muscles on surface electromyography). Differences in cervical sagittal parameters and muscular function in subjects with different cervical spine alignments, and correlations between VAS scores, NDI, cervical sagittal parameters, and muscular function indices were statistically analyzed. Results: The FRR of the splenius capitis (SPL), upper trapezius (UTr), and sternocleidomastoid (SCM) were higher in subjects with cervical lordosis than in subjects with cervical kyphosis. FRRSPL was higher in subjects with C-type kyphosis than in subjects with R- and S-type kyphosis (P < 0.05), and was correlated with VAS scores, Cobb angle, T1S, and SVA. FRRUTr was correlated with NDI, SCA, T1S, and SVA. FRRSCM was correlated with VAS scores and Cobb angle. CCR was correlated with SCA and SVA. Conclusion: Cervical sagittal parameters differed among different cervical kyphosis types. FRRs and CCRs were significantly worse in R-type kyphosis than other kyphosis types. Cervical muscular functions were correlated with cervical sagittal parameters and morphological alignment.

Current Status and Trends of Research on Cervical Spondylotic Myelopathy from the Perspective of Bibliometrics.

This review was performed to analyze the research on cervical spondylotic myelopathy published during the past 25 years, summarize the developments in existing research, and predict future hotspots in the field. The goal is to provide a comprehensive overview and exploration of developments in this research area. A bibliometric analysis was performed using CiteSpace and VOSviewer to quantitatively and visually analyze relevant literature from Web of Science between 1998 and 2023. Co-occurrence analysis and co-citation analysis were conducted to evaluate papers, authors, journals, countries, and keywords. In total, 1886 papers were included. The overall publication output in this field increased throughout the review period. Stable author collaboration groups were formed, with the most influential author being Fehlings M.G. Japan and the United States contributed the highest number of publications. The predicted future research hotspots include risk factor analysis, outcome prediction, and machine learning. This study provides both an overview of the research trajectory in the field of cervical spondylotic myelopathy for scholars interested in this area, as well as offering insights and references for future research directions in the field.

HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation.

Energy metabolism, through pathways such as oxidative phosphorylation (OxPhos) and glycolysis, plays a pivotal role in cellular differentiation and function. Our study investigates the impact of OxPhos disruption in cortical bone development by deleting mitochondrial transcription factor A (TFAM). TFAM controls OxPhos by regulating the transcription of mitochondrial genes. The cortical bone, constituting the long bones' rigid shell, is sheathed by the periosteum, a connective tissue layer populated with skeletal progenitors that spawn osteoblasts, the bone-forming cells. TFAM-deficient mice presented with thinner cortical bone, spontaneous midshaft fractures, and compromised periosteal cell bioenergetics, characterized by reduced ATP levels. Additionally, they exhibited an enlarged periosteal progenitor cell pool with impaired osteoblast differentiation. Increasing hypoxia-inducible factor 1a (HIF1) activity within periosteal cells substantially mitigated the detrimental effects induced by TFAM deletion. HIF1 is known to promote glycolysis in all cell types. Our findings underscore the indispensability of OxPhos for the proper accrual of cortical bone mass and indicate a compensatory mechanism between OxPhos and glycolysis in periosteal cells. The study opens new avenues for understanding the relationship between energy metabolism and skeletal health and suggests that modulating bioenergetic pathways may provide a therapeutic avenue for conditions characterized by bone fragility.

Quasi-Planar Core Based Spiro-Type Hole-Transporting Material for Dopant-Free Perovskite Solar Cells.

Hole-transporting material (HTMs) are crucial for obtaining the stability and high efficiency of perovskite solar cells (PSCs). However, the current state-of-the-art n-i-p PSCs relied on the use of 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD) exhibit inferior intrinsic and ambient stability due to the p-dopant and hydrophilic Li-TFSI additive. In this study, a new spiro-type HTM with a critical quasi-planar core (Z-W-03) is developed to improve both the thermal and ambient stability of PSCs. The results suggest that the planar carbazole structure effectively passivates the trap states compared to the triphenylamine with a propeller-like conformation in spiro-OMeTAD. This passivation effect leads to the shallower trap states when the quasi-planar HTMs interact with the Pb-dimer. Consequently, the device using Z-W-03 achieves a higher Voc of 1.178 V compared to the spiro-OMeTAD's 1.155 V, resulting in an enhanced efficiency of 24.02 %. In addition, the double-column π-π stacking of Z-W-03 results in high hole mobility (~10-4 cm2 V-1 s-1) even without p-dopant. Moreover, when the surface interface is modified, the undoped Z-W-03 device can achieve an efficiency of nearly 23 %. Compared to the PSCs using spiro-OMeTAD, those with Z-W-03 exhibit enhanced stability under N2 and ambient conditions. This superior performance is attributed to the quasi-planar core structure and the presence of multiple CH/π and π-π intermolecular stacking in Z-W-03. The multiple CH/π and π-π intermolecular contacts of HTMs can improve the hole hopping transport. Therefore, it is imperative to focus on further molecular structure design and optimization of spiro-type HTMs incorporating quasi-planar cores and carbazole moieties for the commercialization of PSCs.

Identification and Analysis of the Mechanism of Stem Mechanical Strength Enhancement for Maize Inbred Lines QY1.

Enhancing stalk strength is a crucial strategy to reduce lodging. We identified a maize inbred line, QY1, with superior stalk mechanical strength. Comprehensive analyses of the microstructure, cell wall composition, and transcriptome of QY1 were performed to elucidate the underlying factors contributing to its increased strength. Notably, both the vascular bundle area and the thickness of the sclerenchyma cell walls in QY1 were significantly increased. Furthermore, analyses of cell wall components revealed a significant increase in cellulose content and a notable reduction in lignin content. RNA sequencing (RNA-seq) revealed changes in the expression of numerous genes involved in cell wall synthesis and modification, especially those encoding pectin methylesterase (PME). Variations in PME activity and the degree of methylesterification were noted. Additionally, glycolytic efficiency in QY1 was significantly enhanced. These findings indicate that QY1 could be a valuable resource for the development of maize varieties with enhanced stalk mechanical strength and for biofuel production.

Integrating MRI-based radiomics and clinicopathological features for preoperative prognostication of early-stage cervical adenocarcinoma patients: in comparison to deep learning approach.

OBJECTIVES: The roles of magnetic resonance imaging (MRI) -based radiomics approach and deep learning approach in cervical adenocarcinoma (AC) have not been explored. Herein, we aim to develop prognosis-predictive models based on MRI-radiomics and clinical features for AC patients. METHODS: Clinical and pathological information from one hundred and ninety-seven patients with cervical AC was collected and analyzed. For each patient, 107 radiomics features were extracted from T2-weighted MRI images. Feature selection was performed using Spearman correlation and random forest (RF) algorithms, and predictive models were built using support vector machine (SVM) technique. Deep learning models were also trained with T2-weighted MRI images and clinicopathological features through Convolutional Neural Network (CNN). Kaplan-Meier curve was analyzed using significant features. In addition, information from another group of 56 AC patients was used for the independent validation. RESULTS: A total of 107 radiomics features and 6 clinicopathological features (age, FIGO stage, differentiation, invasion depth, lymphovascular space invasion (LVSI), and lymph node metastasis (LNM) were included in the analysis. When predicting the 3-year, 4-year, and 5-year DFS, the model trained solely on radiomics features achieved AUC values of 0.659 (95%CI: 0.620-0.716), 0.791 (95%CI: 0.603-0.922), and 0.853 (95%CI: 0.745-0.912), respectively. However, the combined model, incorporating both radiomics and clinicopathological features, outperformed the radiomics model with AUC values of 0.934 (95%CI: 0.885-0.981), 0.937 (95%CI: 0.867-0.995), and 0.916 (95%CI: 0.857-0.970), respectively. For deep learning models, the MRI-based models achieved an AUC of 0.857, 0.777 and 0.828 for 3-year DFS, 4-year DFS and 5-year DFS prediction, respectively. And the combined deep learning models got a improved performance, the AUCs were 0.903. 0.862 and 0.969. In the independent test set, the combined model achieved an AUC of 0.873, 0.858 and 0.914 for 3-year DFS, 4-year DFS and 5-year DFS prediction, respectively. CONCLUSIONS: We demonstrated the prognostic value of integrating MRI-based radiomics and clinicopathological features in cervical adenocarcinoma. Both radiomics and deep learning models showed improved predictive performance when combined with clinical data, emphasizing the importance of a multimodal approach in patient management.

Radiotherapy leads to improved overall survival in patients undergoing resection for Undifferentiated pleomorphic sarcoma.

BACKGROUND AND OBJECTIVES: Undifferentiated pleomorphic sarcoma (UPS) is a frequent subtype within the heterogeneous group of soft tissue sarcomas (STS). The use of radiotherapy (RT) has become an important component of a multimodal approach to treating STS. Key studies have demonstrated that the addition of RT improves rates of local control in STS, though the effect on overall survival (OS) is less clear. Furthermore, there is very limited and conflicting evidence regarding effect of RT on overall survival in UPS. The purposes of this investigation were to examine the association between RT and OS in UPS patients undergoing surgical resection and to determine independent prognostic indicators of OS in this patient population. METHODS: This was a retrospective review of patients who underwent surgical treatment for primary UPS from 1993 to 2021. Associations between RT and OS were analyzed with Kaplan-Meier curves and log-rank testing. Cox proportional hazards regression analysis was used to determine independent prognostic factors of OS. RESULTS: One hundred and fourteen patients who underwent surgical resection of primary UPS were included in the study. Ninety-six (84.2 %) patients received RT perioperatively. Use of RT was associated with improved OS on log-rank testing (hazard ratio (HR) 0.20; 95 % confidence interval (CI) 0.11-0.36; p < 0.001). On multivariate analysis, RT was an independent predictor of improved OS (HR 0.18; 95 % CI 0.09-0.39; p < 0.001) while metastasis at presentation (HR 4.82; 95 % CI 2.26-10.27; p < 0.001) and older age (HR 1.92; 95 % CI 1.20-3.36; p = 0.02) were predictive of decreased OS. Use of RT was not significantly associated with a lower rate of local recurrence in our cohort (p = 0.49). CONCLUSIONS: Use of RT in combination with surgery was an independent prognostic indicator of improved overall survival in UPS patients. Older age and metastasis at presentation were associated with worse overall survival. Based on this and other available studies, treatment for UPS should involve limb-sparing resection when feasible with RT to ensure optimal survival.

Prospective, Randomized Controlled Pivotal Trial of Biodegradable Balloon Rectal Spacer for Prostate Radiation Therapy.

PURPOSE/OBJECTIVES: Rectal spacers have been shown to reduce rectal side effects in patients receiving prostate radiation. However, concerns remain regarding precise and reproducible gel injection. We evaluated efficacy and safety of a novel rectoprostatic spacer balloon that allows potential for controlled, adaptable deployment. This study tested co-primary hypotheses: (1) balloon spacer would result in ≥25% reduction of rectal V70 in >75% of subjects and (2) implantation procedure-related and rectal ≥grade 1 adverse events within 6 months (duration ≥2 days, Common Terminology Criteria for Adverse Events 4.0) would be noninferior in balloon versus control subjects. METHODS AND MATERIALS: A total of 222 subjects were enrolled at 16 centers. All patients had T1-T3 prostate cancer without magnetic resonance imaging evidence of posterior extraprostatic invasion. Randomization was 2:1 (balloon: control) and subject-blinded. Patients underwent transperineal transrectal ultrasound axial and sagittal-guided fiducial placement ± balloon, followed by Intensity-Modulated Radiation Therapy (81 Gy in 1.8 Gy fractions or biologically equivalent hypofractionated dose). For efficacy comparisons, plans were generated by a central core lab on pre- and postimplant computed tomography scans. RESULTS: The primary efficacy endpoint was met, with 97.9% of balloon subjects (139/142) having rectal V70 reduction >25% (P < .001). Mean V70 was 7.0 % pre- versus 1.1% postimplant. The primary safety endpoint was met with balloon subjects experiencing fewer ≥grade 1 events, 18% versus 23% (P < .001 for noninferiority). On predefined secondary endpoint of ≥grade 2 events, rates trended lower in balloon subjects (4.3% vs 6.5%, P = .527). Mean perirectal spacing was 19 ± 3.7 mm and maintained through radiation treatment (18 ± 3.9 mm). Balloon resorption was observed on 6-month computed tomography in 98.5% (133/135) of subjects. The Expanded Prostate Cancer Index quality of life instrument was collected throughout study, and did not differ statistically between the study arms. CONCLUSIONS: Biodegradable rectal spacer balloon was effective in significantly reducing dose to rectum, and associated with decreased cumulative rectal plus implantation-related adverse events. Balloon resorption was consistently observed by 6 months.

Generation of an induced pluripotent stem cell line (CSBZZUi001-A) from a female Alzheimer's patient carrying the PSEN1 709 T > C heterozygous mutation.

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

Integration of C3H15-mediated transcriptional and post-transcriptional regulation confers plant thermotolerance in Arabidopsis.

Heat stress is an environmental factor that significantly threatens crop production worldwide. Nevertheless, the molecular mechanisms governing plant responses to heat stress are not fully understood. Plant zinc finger CCCH proteins have roles in stress responses as well as growth and development through protein-RNA, protein-DNA, and protein-protein interactions. Here, we reveal an integrated multi-level regulation of plant thermotolerance that is mediated by the CCCH protein C3H15 in Arabidopsis. Heat stress rapidly suppressed C3H15 transcription, which attenuated C3H15-inhibited expression of its target gene HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2), a central regulator of heat stress response (HSR), thereby activating HEAT SHOCK COGNATE 70 (HSC70.3) expression. The RING-type E3 ligase MED25-BINDING RING-H2 PROTEIN 2 (MBR2) was identified as an interacting partner of C3H15. The mbr2 mutant was susceptible to heat stress compared to wild-type plants, whereas plants overexpressing MBR2 showed increased heat tolerance. MBR2-dependent ubiquitination mediated the degradation of phosphorylated C3H15 protein in the cytoplasm, which was enhanced by heat stress. Consistently, heat sensitivities of C3H15 overexpression lines increased in MBR2 loss-of-function and decreased in MBR2 overexpression backgrounds. Heat stress-induced accumulation of HSC70.3 promoted MBR2-mediated degradation of C3H15 protein, implying that an auto-regulatory loop involving C3H15, HSFA2, and HSC70.3 regulates HSR. Heat stress also led to the accumulation of C3H15 in stress granules (SGs), a kind of cytoplasmic RNA granule. This study advances our understanding of the mechanisms plants use to respond to heat stress, which will facilitate technologies to improve thermotolerance in crops.

Development and Application of a Mitochondrial Genetically Encoded Voltage Indicator in Narcosis.

Mitochondrial membrane potential (MMP) plays a crucial role in the function of cells and organelles, involving various cellular physiological processes, including energy production, formation of reactive oxygen species (ROS), unfolded protein stress, and cell survival. Currently, there is a lack of genetically encoded fluorescence indicators (GEVIs) for MMP. In our screening of various GEVIs for their potential monitoring MMP, the Accelerated Sensor of Action Potentials (ASAP) demonstrated optimal performance in targeting mitochondria and sensitivity to depolarization in multiple cell types. However, mitochondrial ASAPs also displayed sensitivity to ROS in cardiomyocytes. Therefore, two ASAP mutants resistant to ROS were generated. A double mutant ASAP3-ST exhibited the highest voltage sensitivity but weaker fluorescence. Overall, four GEVIs capable of targeting mitochondria were obtained and named mitochondrial potential indicators 1-4 (MPI-1-4). In vivo, fiber photometry experiments utilizing MPI-2 revealed a mitochondrial depolarization during isoflurane-induced narcosis in the M2 cortex.

Waiting for self-healing as a primary management strategy for lower lip mucoceles.

OBJECTIVES: Oral mucoceles are most frequently encountered on the lower lip. A variety of treatment options are currently employed, including surgical excision, pharmacological injections, and laser therapy. However, each of these approaches may introduce risks and potential complications. Clinical practice has demonstrated a potential for self-healing in lower lip mucoceles, making a conservative observational approach more appealing. This research is a prospective study aimed at evaluating the self-healing capacity of lower lip mucoceles. METHODS: In this prospective study, patients with mucoceles were encouraged to intentionally delay medical intervention and to wait for self-healing. Disappearance of the mucocele for at least 3 months was defined as self-healing. RESULTS: Thirty patients with lower lip mucoceles were included. With no intervention, 24 patients (80%) reported self-healing of lower lip mucoceles. The mean natural duration of the mucoceles was 3.63 (± 4.7; 1-24) months. After self-healing of the mucocele, the patients were followed up for 17.21 (± 9.45; 2-30) months and there were no reported recurrences. CONCLUSIONS: Lower lip mucoceles have a high potential for self-healing and patients may be routinely encouraged to wait for self-healing. CLINICAL RELEVANCE: The high self-healing rate observed in this study suggests that a conservative, non-interventional approach might be considered as the first-line management for lower lip mucoceles.

Optimization of Composite Enzymatic Extraction, Structural Characterization and Biological Activity of Soluble Dietary Fiber from Akebia trifoliata Peel.

In order to reduce the waste of Akebia trifoliata peel and maximize its utilization, in this study, on the basis of a single-factor experiment and the response surface method, the optimum technological conditions for the extraction of soluble dietary fiber from Akebia trifoliata peel with the compound enzyme method were obtained. The chemical composition, physical and chemical properties, structural characterization and biological activity of the purified soluble dietary fiber (AP-SDF) from the Akebia trifoliata peel were analyzed. We discovered that that the optimum yield was 20.87% under the conditions of cellulase addition 600 U/g, enzymolysis time 100 min, solid-liquid ratio 1:24 g/mL and enzymolysis temperature 51 °C. At the same time, AP-SDF was a porous network structure cellulose type I acidic polysaccharose mainly composed of arabinoxylan (36.03%), galacturonic acid (27.40%) and glucose (19.00%), which possessed the structural characteristic peaks of the infrared spectra of polysaccharides and the average molecular weight (Mw) was 95.52 kDa with good uniformity. In addition, the AP-SDF exhibited high oil-holding capacity (15.11 g/g), good water-holding capacity and swelling capacity, a certain antioxidant capacity in vitro, hypoglycemic activity in vitro for α-glucosidase inhibition and hypolipidemic activity in vitro for the binding ability of bile acids and cholesterol. These results will provide a theoretical basis for the development of functional products with antioxidant, hypoglycemic and hypolipidemic effects, which have certain application value in related industries.

Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.

DGK5-mediated phosphatidic acid homeostasis interplays with reactive oxygen species in plant immune signaling.

Reactive oxygen species (ROS) and phosphatidic acid (PA) are important second messengers in plant immunity. PA binding to RBOHD, an NADPH oxidase responsible for ROS production, enhances RBOHD stability and promotes ROS production. Distinct phosphorylation of the lipid kinase DGK5 optimizes the PA burst in regulating ROS production.

Neurotransmitter accumulation and Parkinson's disease-like phenotype caused by anion channelrhodopsin opto-controlled astrocytic mitochondrial depolarization in substantia nigra pars compacta.

Parkinson's disease (PD) is a mitochondria-related neurodegenerative disease characterized by locomotor deficits and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Majority of PD research primarily focused on neuronal dysfunction, while the roles of astrocytes and their mitochondria remain largely unexplored. To bridge the gap and investigate the roles of astrocytic mitochondria in PD progression, we constructed a specialized optogenetic tool, mitochondrial-targeted anion channelrhodopsin, to manipulate mitochondrial membrane potential in astrocytes. Utilizing this tool, the depolarization of astrocytic mitochondria within the SNc in vivo led to the accumulation of γ-aminobutyric acid (GABA) and glutamate in SNc, subsequently resulting in excitatory/inhibitory imbalance and locomotor deficits. Consequently, in vivo calcium imaging and interventions of neurotransmitter antagonists demonstrated that GABA accumulation mediated movement deficits of mice. Furthermore, 1 h/day intermittent astrocytic mitochondrial depolarization for 2 weeks triggered spontaneous locomotor dysfunction, α-synuclein aggregation, and the loss of DA neurons, suggesting that astrocytic mitochondrial depolarization was sufficient to induce a PD-like phenotype. In summary, our findings suggest the maintenance of proper astrocytic mitochondrial function and the reinstatement of a balanced neurotransmitter profile may provide a new angle for mitigating neuronal dysfunction during the initial phases of PD.