Chemical Strategies to Diversification of the Mechanical Properties of Organic Crystals.

Structurally ordered soft materials that respond to complementary stimuli are susceptible to control over their spatial and temporal morphostructural configurations via intersectional or combined effects such as gating, feedback, shape-memory, or programming. In absence of general and robust design and prediction strategies for their mechanical properties, at present, combined chemical and crystal engineering approaches could provide useful guidelines to identify effectors that determine both the magnitude and time of their response. Here, we capitalize on the purported ability of soft intermolecular interactions to instigate mechanical compliance by using halogenation to elicit both mechanical and photochemical activity of organic crystals. Starting from (E)-1,4-diphenylbut-2-ene-1,4-dione, whose crystals are brittle and photoinert, we use double and quadruple halogenation to introduce halogen-bonded planes that become interfaces for molecular gliding, rendering the material mechanically and photochemically plastic. Fluorination diversifies the mechanical effects further, and crystals of the tetrafluoro derivative are also elastic but also motile, displaying the rare photosalient effect.

Dietary fat supplementation relieves cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis in pigs.

BACKGROUND: Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation. RESULTS: Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation. CONCLUSIONS: Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.

Alternative splicing analysis of lignocellulose-degrading enzyme genes and enzyme variants in Aspergillus niger.

Alternative splicing (AS) greatly expands the protein diversity in eukaryotes. Although AS variants have been frequently reported existing in filamentous fungi, it remains unclear whether lignocellulose-degrading enzyme genes in industrially important fungi undergo AS events. In this work, AS events of lignocellulose-degrading enzymes genes in Aspergillus niger under two carbon sources (glucose and wheat straw) were investigated by RNA-Seq. The results showed that a total of 23 out of the 56 lignocellulose-degrading enzyme genes had AS events and intron retention was the main type of these AS events. The AS variant enzymes from the annotated endo-ß-1,4-xylanase F1 gene (xynF1) and the endo-ß-1,4-glucanase D gene (eglD), noted as XYNF1-AS and EGLD-AS, were characterized compared to their normal splicing products XYNF1 and EGLD, respectively. The AS variant XYNF1-AS displayed xylanase activity whereas XYNF1 did not. As for EGLD-AS and EGLD, neither of them showed annotated endo-ß-1,4-glucanase activity. Instead, both showed lytic polysaccharide monooxygenase (LPMO) activity with some differences in catalytic properties. Our work demonstrated that the AS variants in A. niger were good sources for discovering novel lignocellulose-degrading enzymes. KEY POINTS: • AS events were identified in the lignocellulose-degrading enzyme genes of A. niger. • New ß-1,4-xylanase and LPMO derived from AS events were characterized.

Robot-assisted laparoscopic retroperitoneal donor nephrectomy: a safe and efficient improvement.

PURPOSE: Reducing operative injuries is important in living donor nephrectomy. The robot-assisted transperitoneal approach has some advantages than traditional laparoscopic techniques. However, longer operation time and risks of abdominal complications indicate the need for improved techniques. The aim of this study is to present the robot-assisted laparoscopic retroperitoneal donor nephrectomy and evaluate its safety and feasibility. METHODS: This was a retrospective study. From June 2016 to December 2020, 218 living donors underwent robot-assisted laparoscopic retroperitoneal donor nephrectomy. Perioperative data such as operation time, warm ischemia time, length of stay and complications were collected and analyzed. To evaluate the feasibility of this surgical technique, the cumulative summation method was used to construct a learning curve. RESULTS: There were 60 male and 158 female donors aged 36-72 years, with an average age of 53.1 ± 6.8 years. Three patients (1.4%) were converted to open surgery. The mean operation time was 115.4 ± 41.9 min, the warm ischemia time was 206.6 ± 146.7 s, and the length of stay was 4.1 ± 1.4 days. Complications were reported in 22 patients (10.1%), three of whom (1.4%) had Clavien‒Dindo IIIa complications. No ileus occurred. No donors were readmitted. Four patients had delayed graft function. The cumulative summation curve showed that the number needed to reach proficiency was 33. The operation time and warm ischemia time after technical proficiency were 100.4 ± 21.6 min and 142.5 ± 50.7 s, respectively. CONCLUSION: Robot-assisted laparoscopic retroperitoneal donor nephrectomy is a safe and efficient technique that offers advantages of shorter operation time and no abdominal organ interference.

Impact of bilateral facet joint violation on radiographic degeneration of superior adjacent segments and clinical outcomes.

OBJECTIVE: Facet joint violation (FJV) is associated with postoperative low-back pain and is a confirmed risk factor for adjacent-segment degeneration, a long-term complication of lumbar fusion surgery. The authors' knowledge of its mechanisms comes from in vitro biomechanical research only; there is a lack of radiographic evidence of the effects of violation on the superior adjacent-segment facet joint, intervertebral disc, and other local radiographic parameters. Furthermore, any differences between unilateral and bilateral violation remain relatively unclear. The authors therefore aimed to explore the effects of nonviolation and unilateral and bilateral violation on radiographic degeneration of the facet joint and intervertebral disc at the fusion and superior adjacent segment. Patient-reported clinical outcomes were compared at the 2-year follow-up. METHODS: The authors retrospectively analyzed data from 148 patients with lumbar degenerative diseases who underwent single-segment minimally invasive transforaminal lumbar interbody fusion between 2016 and 2020. FJV and facet joint degeneration were evaluated and graded using Shah's method and Pathria's standard, respectively. Radiographic parameters, including disc height and intervertebral Cobb angle at the fusion and superior adjacent segment, were measured. Clinical outcomes were evaluated using visual analog scale (VAS) and Japanese Orthopaedic Association scores. RESULTS: Preoperative data were comparable among the 3 groups (nonviolation, unilateral violation, and bilateral violation) (p > 0.05). Patient-reported clinical outcomes were followed up for at least 2 years (average duration 28.17 ± 6.17 months). At the last follow-up, facet joint degeneration grades were sequentially increased in the nonviolation, unilateral violation, and bilateral violation groups (p = 0.006). The unilateral (2.45 ± 2.17 mm) and bilateral (2.70 ± 1.94 mm) violation groups had more severe losses of disc height in the superior adjacent segment than did the nonviolation group (1.31 ± 2.01 mm). The VAS low-back pain and Japanese Orthopaedic Association scores in the bilateral (2.57 ± 1.44 and 19.83 ± 2.84, respectively) and unilateral (2.26 ± 0.79 and 20.43 ± 3.85, respectively) violation groups were significantly worse than in the nonviolation group (1.69 ± 1.12 and 21.80 ± 3.36, respectively) (p < 0.05). By contrast, there were no significant between-group differences in disc height, intervertebral Cobb angle in the fusion segment, or VAS leg pain scores (p > 0.05). CONCLUSIONS: FJV was associated with postoperative low-back pain and worse functional outcomes. It also aggravated facet joint and intervertebral disc changes in the superior adjacent segment, especially when bilateral violation occurred; this may be part of the mechanisms of adjacent-segment degeneration.

Improving drug response prediction via integrating gene relationships with deep learning.

Predicting the drug response of cancer cell lines is crucial for advancing personalized cancer treatment, yet remains challenging due to tumor heterogeneity and individual diversity. In this study, we present a deep learning-based framework named Deep neural network Integrating Prior Knowledge (DIPK) (DIPK), which adopts self-supervised techniques to integrate multiple valuable information, including gene interaction relationships, gene expression profiles and molecular topologies, to enhance prediction accuracy and robustness. We demonstrated the superior performance of DIPK compared to existing methods on both known and novel cells and drugs, underscoring the importance of gene interaction relationships in drug response prediction. In addition, DIPK extends its applicability to single-cell RNA sequencing data, showcasing its capability for single-cell-level response prediction and cell identification. Further, we assess the applicability of DIPK on clinical data. DIPK accurately predicted a higher response to paclitaxel in the pathological complete response (pCR) group compared to the residual disease group, affirming the better response of the pCR group to the chemotherapy compound. We believe that the integration of DIPK into clinical decision-making processes has the potential to enhance individualized treatment strategies for cancer patients.

Structural disorder determines capacitance in nanoporous carbons.

The difficulty in characterizing the complex structures of nanoporous carbon electrodes has led to a lack of clear design principles with which to improve supercapacitors. Pore size has long been considered the main lever to improve capacitance. However, our evaluation of a large series of commercial nanoporous carbons finds a lack of correlation between pore size and capacitance. Instead, nuclear magnetic resonance spectroscopy measurements and simulations reveal a strong correlation between structural disorder in the electrodes and capacitance. More disordered carbons with smaller graphene-like domains show higher capacitances owing to the more efficient storage of ions in their nanopores. Our findings suggest ways to understand and exploit disorder to achieve highly energy-dense supercapacitors.

Risk Factors for Surgical Treatment of Lumbar Degenerative Disc Disease in Middle-aged and Older Women: A Prospective Case-Control Study of 2370 Subjects.

OBJECTIVE: Given the distinct physiological and societal traits between women and men, we propose that there are distinct risk factors for lumbar degenerative disc disease surgeries, including lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS), in middle-aged and older populations. However, few studies have focused on middle-aged and older women. This study aims to identify these risk factors specifically in this population. METHODS: In this case-control study, the study group comprised 1202 women aged ≥ 45 years who underwent operative treatment of lumbar degenerative disc disease (LDH, n = 825; LSS, n = 377), and the control group comprised 1168 women without lumbar disease who visited a health examination clinic during the same period. The study factors included demographics (age, body mass index [BMI], smoking, labor intensity, and genetic history), female-specific factors (menopausal status, number of deliveries, cesarean section, and simple hysterectomy), surgical history (number of abdominal surgeries, hip joint surgery, knee joint surgery, and thyroidectomy), and systemic diseases (hypercholesterolemia, hypertriglyceridemia, hyper-low-density lipoprotein cholesterolemia, hypertension, diabetes, cardiovascular disease, and cerebrovascular disease). Multivariate binary logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) of associated factors. RESULTS: The risk factors for surgical treatment of LDH in middle-aged and older women included BMI (OR = 1.603), labor intensity (OR = 1.189), genetic history (OR = 2.212), number of deliveries (OR = 1.736), simple hysterectomy (OR = 2.511), hypertriglyceridemia (OR = 1.932), and hyper-low-density lipoprotein cholesterolemia (OR = 2.662). For surgical treatment of LSS, the risk factors were age (OR = 1.889), BMI (OR = 1.671), genetic history (OR = 2.134), number of deliveries (OR = 2.962), simple hysterectomy (OR = 1.968), knee joint surgery (OR = 2.527), hypertriglyceridemia (OR = 1.476), hyper-low-density lipoprotein cholesterolemia (OR = 2.413), and diabetes (OR = 1.643). Cerebrovascular disease was a protective factor against surgery for LDH (OR = 0.267). CONCLUSIONS: BMI, genetic history, number of deliveries, simple hysterectomy, hypertriglyceridemia, and hyper-low-density lipoprotein cholesterolemia were independent risk factors for surgical treatment of both LDH and LSS in middle-aged and older women. Two disparities were found: labor intensity was a risk factor for LDH patients, and knee joint surgery and diabetes were risk factors for LSS patients.

Fragmentation characteristics-based nontargeted screening method of exogenous chemical residues in animal-derived foods using reversed-phase and hydrophilic interaction liquid chromatography-high-resolution mass spectrometry.

Fragmentation characteristics are crucial for nontargeted screening to discover and identify unknown exogenous chemical residues in animal-derived foods. In this study, first, fragmentation characteristics of 51 classes of exogenous chemical residues were summarized based on experimental mass spectra of standards in reversed-phase and hydrophilic interaction liquid chromatography-high-resolution mass spectrometry (MS) and mass spectra from the MassBank of North America (MoNA) library. According to the proportion of fragmentation characteristics to the total number of chemical residues in each class, four screening levels were defined to classify 51 classes of chemical residues. Then, a nontargeted screening method was developed based on the fragmentation characteristics. The evaluation results of 82 standards indicated that more than 90 % of the chemical residues with MS/MS spectra can be identified at concentrations of 100 and 500 µg/kg, and about 80 % can be identified at 10 µg/kg. Finally, the nontargeted screening method was applied to 16 meat samples and 21 egg samples as examples. As a result, eight chemical residues and transformation products (TPs) of 5 classes in the exemplary samples were found and identified, in which 3 TPs of azithromycin were identified by fragmentation characteristics-assisted structure interpretation. The results demonstrated the practicability of the nontargeted screening method for routine risk screening of food safety.

Optimal power-heat-carbon scheduling strategy for interconnected heterogeneous multi-microgrid considering hydrogen fuel cell vehicles.

The scale of multi-microgrid (MMG) and hydrogen fuel cell vehicles (HFCVs) is increasing dramatically with the increase in the new energy penetration ratio, and developing an integrated energy system containing a multi-microgrid for hydrogen fuel vehicles brings great challenges to power grid operation. Focusing on the difficulties of the access of multiple microgrids for the low-carbon and economic operation of the system, this paper proposes an optimal interconnected heterogeneous multi-microgrid power-heat-carbon scheduling strategy for hydrogen-fueled vehicles. Firstly, an HFCV model is established, and then an optimal scheduling model is constructed for the cooperative trading of power-heat-carbon in a multi-microgrid, on the basis of which the low-carbon economic operation of the multi-microgrid is realized. The results of the case study show that the scheduling strategy in this paper reduces carbon emissions by about 7.12% and costs by about 3.41% compared with the independent operation of the multi-microgrid. The degrees of interaction of each multi-microgrid are also analyzed under different HFCV penetration rates.

Association of two novel systemic inflammatory biomarkers and frailty based on NHANES 2007-2018.

Background: Frailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States. Methods: This study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot. Results: This study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24-1.54) and 1.69 (1.53-1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55-2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10-1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95-2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty. Conclusion: The results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

Berlin Green with tunable iron content as ultra-high rate host for efficient aqueous ammonium ion storage.

Prussian blue analogues (PBAs) are regarded as promising cathode materials for ammonium-ion batteries (AIBs) because of their low cost and superb theoretical capacity. However, its inherently poor conductivity and structural collapse can significantly limit the enhancement of rate property and cycling stability. In this work, Berlin Green (BG) electrode materials with similar wool-like clusters were constructed by direct precipitation method to accelerate the kinetic, which realizes outstanding cycling stability. Berlin Green with the appropriate amount of iron (BG-2) has a fast ion transport channel, enhanced structure stability, highly reversible insertion/extraction of NH4+, and fine electrochemical reaction activity. Benefiting from the unique architecture and component, the BG-2 electrode shows an excellent rate performance with a discharge/charge specific capacity of 60.1/59.3 mAh g-1 at 5 A g-1. Even at 5 A g-1, BG-2 exhibits remarkable cycling stability with an initial discharge capacity of 59.5 mAh g-1 and a capacity retention rate of approximately 76% after 30,000 cycles. The BG-2 reveals exceedingly good electrochemical reversibility during the process of NH4+ (de)insertion. BG materials indicate huge potential as a cathode material for the next generation of high-performance aqueous batteries.

Effectiveness of prognostic nutritional index in predicting overall survival and evaluating immunotherapy response in anaplastic thyroid carcinoma.

BACKGROUND: The prognostic value of nutritional status in anaplastic thyroid carcinoma (ATC) remains unclear. The Prognostic Nutritional Index (PNI) is a reliable indicator of overall nutritional and immune status, and it has emerged as a significant prognostic factor in various malignancies. This study aimed to explore the utility of PNI in ATC. METHODS: We systematically reviewed ATC patients in our institute from January 2000 to June 2023 and categorized them into high and low PNI groups based on the median PNI value. Kaplan-Meier analysis and Cox regression were employed to assess the impact of PNI on overall survival, while ROC curve analysis evaluated the predictive value of PNI. Mimics software was used for three-dimensional reconstruction of pre- and post-immunotherapy tumor volumes, enabling the assessment of treatment response. RESULTS: A total of 77 ATC patients were included in this study. Low baseline PNI was associated with significantly shorter overall survival (1-year survival rate: 5.26% vs 30.77%; median survival time: 5.30 months vs 8.87 months). The 1-year, 2-year, and 3-year AUC values for PNI were 0.82, 0.79, and 0.77, respectively. In the multivariate analysis, both PNI and tumor size emerged as independent prognostic factors for patient overall survival. Among ATC patients receiving 2-3 cycles of immunotherapy, an increase in post-treatment PNI levels was positively correlated with a reduction in tumor volume. CONCLUSION: PNI is an independent predictor of overall survival and holds the potential to serve as a valuable indicator for assessing and predicting immunotherapy efficacy in ATC patients.

Macular hypoplasia and high myopia in 48, xxyy syndrome: a unique case of 48, xxyy syndrome that presents with high myopia and macular dysplasia.

BACKGROUND: Among sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading to a diverse range of physical, neurocognitive, behavioral, and psychological manifestations. Typical characteristics include a tall stature and infertility. Other phenotypes include congenital heart defects, skeletal anomalies, tremors, obesity, as well as the potential for type 2 diabetes and/or peripheral vascular disease. CASE PRESENTATION: A 6-year-old boy, who had been experiencing progressive vision deterioration in both eyes for the past two years, presented with a history of poor vision, delayed motor skills. The patient was diagnosed with micropenis in the pediatric outpatient clinic. Sparse hair, an unusually tall stature and craniofacial dysmorphology characterized by ocular hypertelorism, depressed nasal bridge, and epicanthic folds were observed. Comprehensive ophthalmic examination revealed high myopia and grade 3 macular hypoplasia. Diagnostic investigations including karyotype analysis and whole-exome sequencing identified an anomalous male karyotype comprising two X and two Y chromosomes, confirming a diagnosis of 48, XXYY syndrome. CONCLUSIONS: This study underscores the rare association of high myopia and grade 3 macular dysplasia with 48, XXYY syndrome. To our knowledge, this case marks the first recorded instance of macular dysplasia in a patient with 48, XXYY syndrome. This novel finding enhances our understanding of this syndrome's phenotypic variability.

Metabolic characterization of sphere-derived prostate cancer stem cells reveals aberrant urea cycle in stemness maintenance.

Alteration of cell metabolism is one of the essential characteristics of tumor growth. Cancer stem cells (CSCs) are the initiating cells of tumorigenesis, proliferation, recurrence, and other processes, and play an important role in therapeutic resistance and metastasis. Thus, identification of the metabolic profiles in prostate cancer stem cells (PCSCs) is critical to understanding prostate cancer progression. Using untargeted metabolomics and lipidomics methods, we show distinct metabolic differences between prostate cancer cells and PCSCs. Urea cycle is the most significantly altered metabolic pathway in PCSCs, the key metabolites arginine and proline are evidently elevated. Proline promotes cancer stem-like characteristics via the JAK2/STAT3 signaling pathway. Meanwhile, the enzyme pyrroline-5-carboxylate reductase 1 (PYCR1), which catalyzes the conversion of pyrroline-5-carboxylic acid to proline, is highly expressed in PCSCs, and the inhibition of PYCR1 suppresses the stem-like characteristics of prostate cancer cells and tumor growth. In addition, carnitine and free fatty acid levels are significantly increased, indicating reprogramming of fatty acid metabolism in PCSCs. Reduced sphingolipid levels and increased triglyceride levels are also observed. Collectively, our data illustrate the comprehensive landscape of the metabolic reprogramming of PCSCs and provide potential therapeutic strategies for prostate cancer.

Risk factors of transient and permanent hypoparathyroidism after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios (OR) were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 mo). Publication bias was assessed using Begg's test, and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery (total thyroidectomy (TT) vs. lobectomy), surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.

CCDC58 is a potential biomarker for diagnosis, prognosis, immunity, and genomic heterogeneity in pan-cancer.

Coiled-coil domain-containing 58 (CCDC58) is a member of the CCDC protein family. Similar to other members, CCDC58 exhibits potential tumorigenic roles in a variety of malignancies. However, there is no systematic and comprehensive pan-cancer analysis to investigate the diagnosis, prognosis, immune infiltration, and other related functions of CCDC58. We used several online websites and databases, such as TCGA, GTEx, UALCAN, HPA, CancerSEA, BioGRID, GEPIA 2.0, TIMER 2.0, and TISIDB, to extract CCDC58 expression data and clinical data of patients in pan-cancer. Then, the relationship between CCDC58 expression and diagnosis, prognosis, genetic alterations, DNA methylation, genomic heterogeneity, and immune infiltration level were determined. In addition, the biological function of CCDC58 in liver hepatocellular carcinoma (LIHC) was investigated. Pan-cancer analysis results showed that CCDC58 was differentially expressed in most tumors and showed excellent performance in diagnosis and prediction of prognosis. The expression of CCDC58 was highly correlated with genetic alterations, DNA methylation, and genomic heterogeneity in some tumors. In addition, the correlation analysis of CCDC58 with the level of immune infiltration and immune checkpoint marker genes indicated that CCDC58 might affect the composition of the tumor immune microenvironment. Enrichment analysis showed that CCDC58-related genes were mainly linked to mitosis, chromosome, and cell cycle. Finally, biological function experiments demonstrated that CCDC58 plays an important role in tumor cell proliferation and migration. CCDC58 was first identified as a pan-cancer biomarker. It may be used as a potential therapeutic target to improve the prognosis of patients in the future.

Elucidation of the Molecular Mechanism of Compound Danshen Dripping Pills Against Angina Pectoris based on Network Pharmacology and Molecular Docking.

BACKGROUND: Compound Danshen dripping pills (CDDP), a traditional Chinese medicine, has had an extensive application in the treatment of angina pectoris (AP) in China. However, research on the bioactive ingredients and underlying mechanisms of CDDP in AP remains unclear. OBJECTIVE: In the present study, we explored the major chemical components and potential molecular mechanisms linked to the anti-angina effects of CDDP through the application of network pharmacology and molecular docking. METHODS: The potential targets of active ingredients in CDDP were sourced from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Swiss Target Prediction Database (STPD). Additionally, targets related to angina pectoris (AP) were retrieved from various databases, including Gene Cards, DisGeNET, Dis Genet, the Drug Bank database (DBD), and the Therapeutic Target Database (TDD). Protein- protein interaction [1] networks were also established, and core targets were identified based on their topological significance. GO enrichment analysis and KEGG pathway analysis were conducted using the R software. Interactions between active ingredients and potential targets selected through the above process were investigated through molecular docking. RESULTS: Seventy-six active ingredients were selected with the following criteria: OB ≥ 30%, DL ≥ 0.18. 383 targets of CDDP and 1488 targets on AP were gathered, respectively. Afterwards, 194 common targets of CDDP and anti-AP targets were defined, of which 12 were core targets. GO enrichment analysis indicated that CDDP acted on AP by response to lipopolysaccharide, regulating the reactive oxygen species and metal ion metabolism, and epithelial cell proliferation. In addition, KEGG enrichment analysis indicated that the signaling pathways were notably enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, and TNF signaling pathway. Moreover, the molecular docking manifested excellent binding capacity between the active ingredients and targets on AP. CONCLUSION: This study comprehensively illustrated the bioactive, potential targets, and molecular mechanisms of CDDP against AP, offering fresh perspectives into the molecular mechanisms of CDDP in preventing and treating AP.

piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis.

The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.

Autistic Traits and Aggressive Behavior in Chinese College Students: A Serial Mediation Model and the Gender Difference.

Background: The existence of aggressive behavior in autism spectrum disorders (ASD) raises questions about whether cognitive and emotional factors in social information processing play a role between autistic traits (ATs) and aggressive behavior in the general population, especially in the context of Chinese culture. Moreover, given a possible gender difference in these variables, the study aimed to examine the effect of ATs on aggressive behavior, and the potential mediating role of hostile attribution bias and alexithymia on this association, as well as gender difference. Methods: 850 Chinese college students participated in the assessment, including their ATs, hostile attribution bias, alexithymia, and aggressive behavior. Pearson correlation, mediation effects analyses, and multiple-group comparison were conducted. Results: The results indicated that ATs indirectly predicted increased aggressive behavior through attribution bias and alexithymia. Gender difference in mediating effects was revealed: ATs indirectly predicted increased aggressive behavior through the serial mediating effect only in males. Conclusion: Hostile attribution bias and alexithymia completely mediated the association between ATs and aggressive behavior, which contained the separate mediating effects of (a) hostile attribution bias and (b) alexithymia and the serial mediating effect of (c) hostile attribution bias and alexithymia. Gender differences in mediating effects were found only in the serial mediating effect, which was significant in males but not in females. The findings revealed the internal mechanism of ATs affecting aggressive behavior and gender difference, which have implications for the intervention of aggressive behavior of individuals with autism and those with high levels of ATs.