Genes associated with cellular senescence as diagnostic markers of major depressive disorder and their correlations with immune infiltration.

Background: Emerging evidence links cellular senescence to the pathogenesis of major depressive disorder (MDD), a life-threatening and debilitating mental illness. However, the roles of cellular senescence-related genes in MDD are largely unknown and were investigated in this study using a comprehensive analysis. Methods: Peripheral blood microarray sequencing data were downloaded from Gene Expression Omnibus (GEO) database and retrieved cellular senescence-related genes from CellAge database. A weighted gene co-expression network analysis was used to screen MDD-associated genes. Protein-protein interactions (PPI) were predicted based on STRING data, and four topological algorithms were used to identify hub genes from the PPI network. Immune infiltration was evaluated using CIBERSORT, followed by a correlation analysis between hub genes and immune cells. Results: A total of 84 cell senescence-related genes were differentially expressed in patients with MDD compared to healthy control participants. Among the 84 genes, 20 were identified to be associated with the MDD disease phenotype, and these genes were mainly involved in hormone-related signaling pathways (such as estrogen, steroid hormone, and corticosteroid) and immune and inflammatory pathways. Three genes, namely, JUN, CTSD, and CALR, which were downregulated in MDD, were identified as the hub genes. The expression of hub genes significantly moderate correlated with multiple immune cells, such as Tregs, NK cells, and CD4+ T cells, and the abundance of these immune cells markedly differed in MDD samples. Multiple microRNAs, transcription factors, and small-molecule drugs targeting hub genes were predicted to explore their molecular regulatory mechanisms and potential therapeutic value in MDD. Conclusion: JUN, CTSD, and CALR were identified as potential diagnostic markers of MDD and may be involved in the immunoinflammatory mechanism of MDD.

Totally laparoscopic versus laparoscopy-assisted distal gastrectomy: the KLASS-07, a randomized controlled trial.

BACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). We performed an RCT to confirm if TLDG is different from LADG. METHODS: The KLASS-07 trial is a multicentre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enrolled from 21 cancer care centers in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was QoL for 1 year. This trial is registered at ClinicalTrials.gov (NCT NCT03393182). RESULTS: 442 patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complication but has advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months.

Brunonianines D-F, three new C19-diterpenoid alkaloids from the Delphinium brunonianum, with therapeutic effect on ovarian cancer in vitro and in vivo.

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.

Correlation between CEUS LI-RADS categorization of HCC < 20 mm and clinic-pathological features.

OBJECTIVE: To retrospectively evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) LI-RADS in liver nodules < 20 mm at high risk of hepatocellular carcinoma (HCC) and their correlation with clinic-pathological features. METHODS: A total of 432 pathologically proved liver nodules < 20 mm were included from January 2019 to June 2022. Each nodule was categorized as LI-RADS grade (LR)-1 to LR-5 through LR-M according to CEUS LI-RADS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of CEUS LI-RADS were evaluated using pathological reference standard. Correlations between clinic-pathological features and CEUS LI-RADS categorization, together with major CEUS features, were further explored. RESULTS: With LR-5 to diagnose HCC, the sensitivity, specificity, PPV, NPV, and AUC were 50.3%, 70.0%, 91.2%, 18.5%, and 0.601, respectively. The proportion of LR-5 in primary HCCs was significantly higher than that in recurrent ones (p = 0.014). HCC 10-19 mm showed significantly more frequent arterial phase hyper-enhancement (APHE) and late washout (p < 0.05) and less no-washout (p = 0.003) compared with those in HCC < 10 mm. Well-differentiated HCCs showed more frequent non-APHE and no-washout than moderate- and poor-differentiated HCCs (p < 0.05). Upgrading "APHE without washout" LR-4 nodules 10-19 mm with HCC history and "APHE with late mild washout" LR-4 nodules < 10 mm to LR-5 could improve the diagnostic performance of LR-5. The corresponding sensitivity, specificity, PPV, NPV, and AUC are 60.2%, 70.0%, 92.6%, 22.1%, and 0.651, respectively. CONCLUSIONS: CEUS LI-RADS is valuable in the diagnosis of HCC < 20 mm and performance can be improved with the combination of clinic-pathological features. CRITICAL RELEVANCE STATEMENT: CEUS LI-RADS was valuable in the diagnosis of HCC < 20 mm and its diagnostic performance can be improved by combining clinic-pathological features. Further research is needed to define its value in this set of lesions. KEY POINTS: Contrast-enhanced ultrasound can detect small liver lesions where LI-RADS accuracy is uncertain. Many LI-RADS Grade-4 nodules were upgraded to Grade-5 by combining imaging with clinic-pathological factors. The reclassification of LI-RADS Grade-5 can improve sensitivity without decreasing positive predictive value.

Sampled-Data H∞ Dynamic Output-Feedback Control for NCSs With Successive Packet Losses and Stochastic Sampling.

The problem of sampled-data H∞ dynamic output-feedback control for networked control systems with successive packet losses (SPLs) and stochastic sampling is investigated in this article. The aim of using sampled-data control techniques is to alleviate network congestion. SPLs that occur in the sensor-to-controller (S-C) and controller-to-actuator (C-A) channels are modeled using a packet loss model. Additionally, it is assumed that stochastic sampling follows a Bernoulli distribution. A model is established to capture the stochastic characteristics of both the SPL model and stochastic sampling. This model is crucial as it allows us to determine the probability distribution of the sampling interval between successive update instants, which is essential for stability analysis. An exponential mean-square stability condition for the constructed equivalent discrete-time stochastic system, which also guarantees the prescribed H∞ performance, is established by incorporating probability theory. The desired controller is designed using a step-by-step synthesis approach, which may offer lower design conservatism compared to some existing methods. Finally, our designed approach using a networked F-404 engine system model is validated and its merits relative to existing results are discussed. The proposed method is finally validated by employing a networked model of the F-404 engine system. Furthermore, the advantages of our method are presented in comparison to previous results.

Quantitative phosphoproteomic analysis of chicken DF-1 cells infected with Eimeria tenella, using tandem mass tag (TMT) and parallel reaction monitoring (PRM) mass spectrometry.

Eimeria tenella is an obligate intracellular parasite which causes great harm to the poultry breeding industry. Protein phosphorylation plays a vital role in host cell-E. tenella interactions. However, no comprehensive phosphoproteomic analyses of host cells at various phases of E. tenella infection have been published. In this study, quantitative phosphoproteomic analysis of chicken embryo DF-1 fibroblasts that were uninfected (UI) or infected with E. tenella for 6 h (PI6, the early invasion phase) or 36 h (PI36, the trophozoite development phase) was conducted. A total of 10,122 phosphopeptides matched to 3,398 host cell phosphoproteins were identified and 13,437 phosphorylation sites were identified. Of these, 491, 1,253, and 275 differentially expressed phosphorylated proteins were identified in the PI6/UI, PI36/UI, and PI36/PI6 comparisons, respectively. KEGG pathway enrichment analysis showed that E. tenella modulated host cell processes through phosphorylation, including focal adhesion, regulation of the actin cytoskeleton, and FoxO signaling to support its early invasion phase, and modulating adherens junctions and the ErbB signaling pathway to favor its trophozoite development. These results enrich the data on the interaction between E. tenella and host cells and facilitate a better understanding of the molecular mechanisms underlying host-parasite relationships.

Title: Analyse phosphoprotéomique quantitative de cellules DF-1 de poulet infectées par Eimeria tenella, par spectrométrie de masse avec marqueur de masse en tandem (TMT) et surveillance des réactions parallèles (PRM). Abstract: Eimeria tenella est un parasite intracellulaire obligatoire qui cause de graves dommages à l'industrie de l'élevage de volailles. La phosphorylation des protéines joue un rôle essentiel dans les interactions entre la cellule hôte et E. tenella. Cependant, aucune analyse phosphoprotéomique complète des cellules hôtes à différentes phases de l'infection par E. tenella n'a été publiée. Dans cette étude, une analyse phosphoprotéomique quantitative de fibroblastes DF-1 d'embryon de poulet non infectés (NI) ou infectés par E. tenella pendant 6 h (PI6, la phase d'invasion précoce) ou 36 h (PI36, la phase de développement des trophozoïtes) a été réalisée. Un total de 10 122 phosphopeptides correspondant à 3 398 phosphoprotéines de cellules hôtes ont été identifiés et 13 437 sites de phosphorylation ont été identifiés. Parmi celles-ci, 491, 1 253 et 275 protéines différentiellement phosphorylées exprimées ont été identifiées respectivement dans les comparaisons PI6/NI, PI36/NI et PI36/PI6. L'analyse d'enrichissement de la voie KEGG a montré qu'E. tenella modulait les processus de la cellule hôte par phosphorylation, y compris l'adhésion focale, la régulation du cytosquelette d'actine et la signalisation FoxO, pour aider sa phase d'invasion précoce, et la modulation des jonctions adhérentes et de la voie de signalisation ErbB pour favoriser le développement de son trophozoïte. Ces résultats enrichissent les données sur l'interaction entre E. tenella et les cellules hôtes et facilitent une meilleure compréhension des mécanismes moléculaires sous-jacents aux relations hôtes­parasites.

Subtype prediction of intrahepatic cholangiocarcinoma using dynamic contrast-enhanced ultrasound.

OBJECTIVE: The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). METHODS: This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. RESULTS: In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort. CONCLUSIONS: Preoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC. CRITICAL RELEVANCE STATEMENT: DCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes. KEY POINTS: Preoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making. Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype. DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.

Clinical characteristics, radiological features and outcomes in pulmonary involvement of cryoglobulinemia.

BACKGROUND: Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood. METHODS: Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia. RESULTS: The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P < 0.0001). CONCLUSIONS: A diagnosis of pulmonary involvement should be highly suspected for patients with cryoglobulinemia and chest CT-indicated infiltrates without other explanations. Patients with pulmonary involvement had a poor prognosis. Rituximab-based treatment may improve the outcome.

A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.

METTL3, a primary methyltransferase catalyzing the RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition. However, current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of the RNA m6A modification. Among candidate peptides, RM3 exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation. We then designed a stapled peptide inhibitor (RSM3) with enhanced peptide stability and formation of the α-helical secondary structure required for METTL3 interaction. Functional and transcriptomic analysis in vivo indicated that RSM3 induced upregulation of programmed cell death-related genes while inhibiting cancer-promoting signals. Furthermore, tumor growth was significantly suppressed while apoptosis was enhanced upon RSM3 treatment, accompanied by increased METTL3 degradation, and reduced global RNA methylation levels in two in vivo tumor models. This peptide inhibitor thus exploits a mechanism distinct from other small-molecule competitive inhibitors to inhibit oncogenic METTL3 activity. Our findings collectively highlight the potential of targeting METTL3 in cancer therapies through peptide-based inhibition of complex formation and proteolytic degradation.

Advancements in de Quervain Tenosynovitis Management: A Comprehensive Network Meta-Analysis.

PURPOSE: This study presents a network meta-analysis aimed at evaluating nonsurgical treatment modalities for de Quervain tenosynovitis. The primary objective was to assess the comparative effectiveness of nonsurgical treatment options. METHODS: The systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches were performed in multiple databases, and studies meeting predefined criteria were included. Data extraction, risk of bias assessment, and statistical analysis were carried out to compare treatment modalities. The analysis was categorized into short-term (within six weeks), medium-term (six weeks up to six months), and long-term (one year) follow-up. RESULTS: The analysis included 14 randomized controlled trials encompassing various treatment modalities for de Quervain tenosynovitis. In the short-term, extracorporeal shockwave therapy demonstrated statistically significant improvement in visual analog scale pain scores compared with placebo. Extracorporeal shockwave therapy also ranked highest in the treatment options based on its treatment effects. Corticosteroid injections (CSIs) combined with casting and laser therapy with orthosis showed favorable outcomes. Corticosteroid injection alone, platelet-rich plasma injections alone, acupuncture, and orthosis alone did not significantly differ from placebo in visual analog scale pain score. In the medium-term, extracorporeal shockwave therapy remained the top-ranking option for visual analog scale pain score, followed by CSI with casting. In the long-term (one year), CSI alone and platelet-rich plasma injections demonstrated sustained pain relief. Combining CSI with orthosis also appeared promising when compared with CSI alone. CONCLUSIONS: Corticosteroid injection with a short duration of immobilization remains the primary and effective treatment for de Quervain tenosynovitis. Extracorporeal shockwave therapy can be considered a secondary option. Alternative treatment modalities, such as isolated therapeutic injection, should be approached with caution because they did not show substantial benefits over placebo. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

A Novel Set-Based Discrete Particle Swarm Optimization for Wastewater Treatment Process Effluent Scheduling.

With the escalating severity of environmental pollution caused by effluent, the wastewater treatment process (WWTP) has gained significant attention. The wastewater treatment efficiency and effluent quality are significantly impacted by effluent scheduling that adjusts the hydraulic retention time. However, the sequential batch and continuous nature of the effluent pose challenges, resulting in complex scheduling models with strong constraints that are difficult to tackle using existing scheduling methods. To optimize maximum completion time and effluent quality simultaneously, this article proposes a restructured set-based discrete particle swarm optimization (RS-DPSO) algorithm to address the WWTP effluent scheduling problem (WWTP-ESP). First, an effective encoding and decoding method is designed to effectively map solutions to feasible schedules using temporal and spatial information. Second, a restructured set-based discrete particle swarm algorithm is introduced to enhance the searching ability in discrete solution space via restructuring the solution set. Third, a constraint handling strategy based on violation degree ranking is designed to reduce the waste of computational resources. Fourth, a Sobel filter based local search is proposed to guide particle search direction to enhance search efficiency ability. The RS-DPSO provides a novel method for solving WWTP-ESP problems with complex discrete solution space. The comparative experiments indicate that the novel designs are effective and the proposed algorithm has superior performance over existing algorithms in solving the WWTP-ESP.

Peritoneal Washing Cytology Positivity in Gastric Cancer: Role of Lymph Node Metastasis as a Risk Factor.

PURPOSE: Peritoneal washing cytology (PWC) is a widely used diagnostic tool for detecting peritoneal metastasis of advanced gastric cancer. However, the prognosis of patients with positive PWC remains poor even after gastrectomy, and treatments vary among institutions and eras. In this study, we identified the clinical factors that can help predict cytology-positive (CY(+)) gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed the national data of patients with gastric cancer from 2019, as provided by the Information Committee of the Korean Gastric Cancer Association. Of the 13,447 patients with gastric cancer, 3,672 underwent PWC. Based on cytology results, we analyzed the clinicopathological characteristics and assessed the possibility of CY(+) outcomes in relation to T and N stages. RESULTS: Of the 3,270 patients who underwent PWC without preoperative chemotherapy, 325 were CY(+), whereas 2,945 were negative. CY(+) was more commonly observed in patients with Borrmann type IV gastric cancer, an undifferentiated histological type, and advanced pathological stages. Multivariate analysis revealed Borrmann type IV (odds ratio [OR], 1.821), tumor invasion to T3-4 (OR, 2.041), and lymph node metastasis (OR, 3.155) as independent predictors of CY(+). Furthermore, for circular tumor location, the N stage emerged as a significant risk factor for CY(+), particularly when the tumor was located on the posterior wall (PW) side. CONCLUSIONS: Lymph node metastasis significantly affects CY(+) outcomes, particularly when the tumor is located on the PW side. Therefore, PWC should be considered not only in suspected serosal exposure cases but also in cases of lymph node metastasis.

Positive effects of parent-child group emotional regulation and resilience training on nonsuicidal self-injury behavior in adolescents: a quasi-experimental study.

Background: Nonsuicidal self-injury (NSSI) among adolescents is a growing global concern. However, effective interventions for treating NSSI are limited. Method: A 36-week quasi-experimental study design of parent-child group resilience training (intervention group) for adolescents aged 12-17 years was used and compared with treatment-as-usual (control group). The primary endpoint was the frequency of NSSI assessed with the Ottawa Self-Injury Inventory (OSI), and the secondary endpoints were the levels of depression, hope, resilience, and family adaptability and cohesion as assessed by the 24-item Hamilton depression rating scale (HAMD-24), Herth Hope Scale (HHS), Connor-Davidson Resilience Scale (CD-RISC), and Family Adaptability and Cohesion Evaluation Scale, second edition (FACES-II-CV), respectively. Result: A total of 118 participants completed the trial. Both groups showed a significant reduction in NSSI frequency after 12, 24, and 36 weeks of intervention (p< 0.05), although the intervention group did not differ significantly from the control group. After 12, 24, and 36 weeks of intervention, the CD-RISC, HHS, HAMD-24, and FACES-II-CV scores in the intervention and control groups improved over baseline (p< 0.05). Furthermore, the intervention group had higher scores on the CD-RISC, HHS, and FACES-II-CV and lower scores on the HAMD-24 than the control group after 12, 24, and 36 weeks of intervention (p  < 0.05). Conclusion: Parent-child group emotional regulation and resilience training showed promise as treatment options for NSSI among adolescents, leading to increased hope, resilience, and improved family dynamics among NSSI teens. Moreover, NSSI frequency significantly decreased in the intervention group compared to baseline.

Two heat shock cognate 70 genes involved in spermatogenesis regulate the male fertility of Zeugodacus cucurbitae, as potential targets for pest control.

The melon fly Zeugodacus cucurbitae Coquillett (Diptera: Tephritidae) is an agricultural quarantine pest threatening fruit and vegetable production. Heat shock cognate 70 (Hsc70), which is a homolog of the heat shock protein 70 (Hsp70), was first discovered in mice testes and plays an important role in spermatogenesis. In this study, we identified and cloned five Hsc70 genes from melon fly, namely ZcHsc70_1/2/3/4/5. Phylogenetic analysis showed that these proteins are closely related to Hsc70s from other Diptera insects. Spatiotemporal expression analysis showed that ZcHsc70_1 and ZcHsc70_2 are highly expressed in Z. cucurbitae testes. Fluorescence in situ hybridization further demonstrated that ZcHsc70_1 and ZcHsc70_2 are expressed in the transformation and maturation regions of testes, respectively. Moreover, RNA interference-based suppression of ZcHsc70_1 or ZcHsc70_2 resulted in a significant decrease of 74.61% and 63.28% in egg hatchability, respectively. Suppression of ZcHsc70_1 expression delayed the transformation of sperm cells to mature sperms. Meanwhile, suppression of ZcHsc70_2 expression decreased both sperm cells and mature sperms by inhibiting the meiosis of spermatocytes. Our findings show that ZcHsc70_1/2 regulates spermatogenesis and further affects the male fertility in the melon fly, showing potential as targets for pest control in sterile insect technique by genetic manipulation of males.

Comparison of Interventions for Lateral Elbow Tendinopathy: A Systematic Review and Network Meta-Analysis for Patient-Rated Tennis Elbow Evaluation Pain Outcome.

PURPOSE: There is controversy regarding the optimal treatment for lateral elbow tendinopathy (LET), and not all available treatment options have been compared directly with placebo/control. A network meta-analysis was conducted to compare the effectiveness of different LET treatments directly and indirectly against control/placebo based on a validated outcome, the Patient-Rated Tennis Elbow Evaluation (PRTEE) pain score. METHODS: Randomized, controlled trials comparing different treatment methods for LET were included, provided they reported outcome data using the PRTEE pain score. A network meta-analysis with random effect was used to combine direct and indirect evidence between treatments compared with placebo in the short term (up to six weeks) and midterm (more than six weeks and up to six months) after intervention. RESULTS: Thirteen studies with 12 comparators including control/placebo were eligible. The results indicated no significant improvement in PRTEE pain score in the short term across all treatments compared with control/placebo. In the midterm, physiotherapy/exercise showed benefit against placebo (mean difference: -4.32, 95% confidence interval: -7.58 and -1.07). Although steroid injections, dry needling, and autologous blood also exhibited potential treatment effects, it is crucial for the clinician to consider certain pitfalls when considering these treatments. The limited number of small studies and paucity of data call for caution in interpreting the results and need for further evidence. CONCLUSIONS: Patients should be informed that there is currently no strong evidence that any treatment produces more rapid improvement in pain symptoms when compared with control/placebo in the short and medium terms. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Visualized in-sensor computing.

In artificial nervous systems, conductivity changes indicate synaptic weight updates, but they provide limited information compared to living organisms. We present the pioneering design and production of an electrochromic neuromorphic transistor employing color updates to represent synaptic weight for in-sensor computing. Here, we engineer a specialized mechanism for adaptively regulating ion doping through an ion-exchange membrane, enabling precise control over color-coded synaptic weight, an unprecedented achievement. The electrochromic neuromorphic transistor not only enhances electrochromatic capabilities for hardware coding but also establishes a visualized pattern-recognition network. Integrating the electrochromic neuromorphic transistor with an artificial whisker, we simulate a bionic reflex system inspired by the longicorn beetle, achieving real-time visualization of signal flow within the reflex arc in response to environmental stimuli. This research holds promise in extending the biomimetic coding paradigm and advancing the development of bio-hybrid interfaces, particularly in incorporating color-based expressions.

CRISPR/Cas9-mediated knockout of a male accessory glands-specific gene takeout1 decreases the fecundity of Zeugodacus cucurbitae female.

BACKGROUND: The melon fly, Zeugodacus cucurbitae (Coquillett), is an invasive Tephritidae pest with robust fertility. The male accessory glands (MAGs) form a vital organ that ensures insect reproductive efficiency. Most of the secreted proteins by MAGs exhibit a male bias expression. Takeout, one of these proteins, is abundantly present in the MAGs of many insects. RESULTS: In this study, we identified 32 takeout genes in Z. cucurbitae. The phylogenetic analysis and multiple sequence alignment results showed that Zctakeout1 is the most related homolog to the MAGs-specific takeout in Tephritidae. The real-time quantitative PCR results showed that Zctakeout1 was exclusively expressed in the male adult stage, and its expression level gradually increased with the increase in age and then remained stable at the sexually matured stage. The distribution among tissues demonstrated the specific expression of Zctakeout1 in the MAGs, and fluorescence immunohistochemical results confirmed the presence of Zctakeout1 in close proximity to binuclear cells of the mesoderm epidermal MAGs. In continuation, CRISPR/Cas9-mediated genome editing was employed, resulting in successfully generating a homozygous strain with an +8 bp insertion. The mating experiments with the Zctakeout1-/- males resulted in significant reductions in both the mating rate and egg production of females. CONCLUSION: These findings prove that the MAGs-specific Zctakeout1 is essential in regulating fecundity in female Z. cucurbitae fruit flies. Our data suggests its utilization in future essential insect-specific gene-directed sterility insect technique (SIT) by the genetic manipulation to keep these important Tephritidae populations under control. © 2024 Society of Chemical Industry.

Chemical constituents of Rubia tibetica Hook. f. from Tibetan medicine and cytotoxic activity evaluation.

Two unprecedented quinone compounds Rubiaxylm A (1) and Rubiaxylm B (2), along with fifteen known anthraquinones (3-17) were isolated and characterized from the roots of Rubia tibetica in Tibetan medicine. Their structures were identified through comprehensive analyses of 1D/2D NMR as well as HR-ESIMS data. Furthermore, all separated compounds were evaluated for their cytotoxic activity on A549, Caco-2, MDA-MB-231 and Skov-3 cell lines. In particular, compound 2 effectively inhibited MDA-MB-231 cells with an IC50 value of 8.15 ± 0.20 µM. Subsequently, the anti-tumor mechanism of 2 was investigated by flow cytometry, JC-1 staining, cell scratching and cell colony. These results indicated that compound 2 could inhibit the proliferation of MDA-MB-231 cells by arresting cells in the G1 phase.

Surgical management of cubital tunnel syndrome: A systematic review and meta-analysis of randomised trials.

Background: Cubital tunnel syndrome (CUTS) is a common upper limb compression neuropathy with significant consequences when left untreated. Surgical decompression remains gold-standard treatment for moderate to severe disease, however the optimal operative technique remains unclear. This network meta-analysis (NMA) of Level I and II randomised prospective studies aims to discern superiority between open in-situ, endoscopic and anterior transposition (subcutaneous or submuscular techniques) with respect to the primary outcome of response-to-treatment and secondary outcomes which include complications, post-operative chronic pain VAS scale, return to work and re-operation. Methods: This NMA adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Web of Science, Cochrane Central, Science direct and Embase were searched. The MESH database was further searched with the terms 'cubital tunnel' to improve sensitivity of the search. Data pertaining to the primary and secondary outcomes were pooled for NMA. Results: Following abstract and full-text screening, 10 randomised prospective trials were included. There was no statistical difference in the response-to-treatment between the four studied techniques. Endoscopic decompression conferred a significantly higher complication rate compared to open decompression (Odds Ratio [OR], 4.21; 95% CI, 1.22-14.59). Endoscopic decompression had a statistically significant lower risk of post-operative chronic pain compared to open in-situ decompression (OR, 0.03, 95% CI, 0.00-0.32). There were no differences between techniques with respect to return to work or re-operation rates. Conclusion: Response-to-treatment was similar between the four operative techniques for CUTS. Endoscopic decompression was found to be more hazardous when compared to open-in situ decompression but conferred significantly less post-operative chronic pain. There was significant heterogeneity in reported outcomes between the included articles. The authors suggest conducting more high-quality research with standardised outcome reporting to facilitate comparison. Level of evidence ii: Systematic Review and Meta-analysis of Randomised Prospective Trials- Therapeutic study.

Automatic detection of thyroid nodules with a real-time artificial intelligence system in a real clinical scenario and the associated influencing factors.

BACKGROUND: At present, most articles mainly focused on the diagnosis of thyroid nodules by using artificial intelligence (AI), and there was little research on the detection performance of AI in thyroid nodules. OBJECTIVE: To explore the value of a real-time AI based on computer-aided diagnosis system in the detection of thyroid nodules and to analyze the factors influencing the detection accuracy. METHODS: From June 1, 2022 to December 31, 2023, 224 consecutive patients with 587 thyroid nodules were prospective collected. Based on the detection results determined by two experienced radiologists (both with more than 15 years experience in thyroid diagnosis), the detection ability of thyroid nodules of radiologists with different experience levels (junior radiologist with 1 year experience and senior radiologist with 5 years experience in thyroid diagnosis) and real-time AI were compared. According to the logistic regression analysis, the factors influencing the real-time AI detection of thyroid nodules were analyzed. RESULTS: The detection rate of thyroid nodules by real-time AI was significantly higher than that of junior radiologist (P = 0.013), but lower than that of senior radiologist (P = 0.001). Multivariate logistic regression analysis showed that nodules size, superior pole, outside (near carotid artery), close to vessel, echogenicity (isoechoic, hyperechoic, mixed-echoic), morphology (not very regular, irregular), margin (unclear), ACR TI-RADS category 4 and 5 were significant independent influencing factors (all P < 0.05). With the combination of real-time AI and radiologists, junior and senior radiologist increased the detection rate to 97.4% (P < 0.001) and 99.1% (P = 0.015) respectively. CONCLUSONS: The real-time AI has good performance in thyroid nodule detection and can be a good auxiliary tool in the clinical work of radiologists.