Effect of Acupuncture on Neurogenic Claudication Among Patients With Degenerative Lumbar Spinal Stenosis : A Randomized Clinical Trial.

BACKGROUND: Acupuncture may improve degenerative lumbar spinal stenosis (DLSS), but evidence is insufficient. OBJECTIVE: To investigate the effect of acupuncture for DLSS. DESIGN: Multicenter randomized clinical trial. (ClinicalTrials.gov: NCT03784729). SETTING: 5 hospitals in China. PARTICIPANTS: Patients with DLSS and predominantly neurogenic claudication pain symptoms. INTERVENTION: 18 sessions of acupuncture or sham acupuncture (SA) over 6 weeks, with 24-week follow-up after treatment. MEASUREMENTS: The primary outcome was change from baseline in the modified Roland-Morris Disability Questionnaire ([RMDQ] score range, 0 to 24; minimal clinically important difference [MCID], 2 to 3). Secondary outcomes were the proportion of participants achieving minimal (30% reduction from baseline) and substantial (50% reduction from baseline) clinically meaningful improvement per the modified RMDQ. RESULTS: A total of 196 participants (98 in each group) were enrolled. The mean modified RMDQ score was 12.6 (95% CI, 11.8 to 13.4) in the acupuncture group and 12.7 (CI, 12.0 to 13.3) in the SA group at baseline, and decreased to 8.1 (CI, 7.1 to 9.1) and 9.5 (CI, 8.6 to 10.4) at 6 weeks, with an adjusted difference in mean change of -1.3 (CI, -2.6 to -0.03; P = 0.044), indicating a 43.3% greater improvement compared with SA. The between-group difference in the proportion of participants achieving minimal and substantial clinically meaningful improvement was 16.0% (CI, 1.6% to 30.4%) and 12.6% (CI, -1.0% to 26.2%) at 6 weeks. Three cases of treatment-related adverse events were reported in the acupuncture group, and 3 were reported in the SA group. All events were mild and transient. LIMITATION: The SA could produce physiologic effects. CONCLUSION: Acupuncture may relieve pain-specific disability among patients with DLSS and predominantly neurogenic claudication pain symptoms, although the difference with SA did not reach MCID. The effects may last 24 weeks after 6-week treatment. PRIMARY FUNDING SOURCE: 2019 National Administration of Traditional Chinese Medicine "Project of building evidence-based practice capacity for TCM-Project BEBPC-TCM" (NO. 2019XZZX-ZJ).

"Rigid-Flexible" Dual-Ferrocene Chimeric Nanonetwork for Simultaneous Tumor-Targeted Tracing and Photothermal/Photodynamic Therapy.

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

Sono-promoted piezocatalysis and low-dose drug penetration for personalized therapy via tumor organoids.

Chemotherapy is a widely used cancer treatment, however, it can have notable side effects owing to the high-doses of drugs administered. Sonodynamic therapy (SDT) induced by sonosensitizers has emerged as a promising approach to treat cancer, however, there is limited research evaluating its therapeutic effects on human tumors. In this study, we introduced a dual therapy that combines low-dose chemotherapeutic drugs with enhanced sonodynamic therapy, utilizing barium titanate (BaTiO3, BTO) nanoparticles (NPs) as sonosensitizers to treat tumor organoids. We demonstrated that ultrasound could improve the cellular uptake of chemotherapy drugs, while the chemotherapeutic effect of the drugs made it easier for BTO NPs to enter tumor cells, and the dual therapy synergistically inhibited tumor cell viability. Moreover, different patient-derived tumor organoids exhibited different sensitivities to this therapy, highlighting the potential to evaluate individual responses to combination therapies prior to clinical intervention. Furthermore, this dual therapy exhibited therapeutic effects equivalent to those of high-dose chemotherapy drugs on drug-resistant tumor organoids and showed the potential to enhance the efficacy of killing drug-resistant tumors. In addition, the biosafety of the BTO NPs was successfully verified in live mice via oral administration. This evidence confirms the reliable and safe nature of the dual therapy approach, making it a feasible option for precise and personalized therapy in clinical applications.

Predicting Acupuncture Efficacy in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Study on Model Development and Result Visualization.

INTRODUCTION: Acupuncture is one of primary treatment options for Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS), but its efficacy varies among patients. This study aimed to develop and validate a nomogram for predicting the efficacy of acupuncture in CP/CPPS. METHODS: This study enrolled 220 patients with CP/CPPS who received acupuncture. Patients were divided into a responder group and non-responder group based on the reduction in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). A nomogram was established using least absolute shrinkage and selection operator logistic regression analysis. The performance of the nomogram was assessed by the receiver operating characteristic curves and calibration curves. RESULTS: 220 men were randomly assigned to the training cohort (n=154) and the internal test cohort (n=66). The developed nomogram included age, current drinking status, sedentary lifestyle, habit of staying up late, expectations for acupuncture, comorbidities, NIH-CPSI pain subscale and total scores. The area under the curve of the prediction model was 0.777 (95%CI: 0.702 to 0.851) in the training cohort, 0.752 (95%CI: 0.616 to 0.888) in the internal test cohort, demonstrating satisfactory discriminative ability as indicated by the calibration curve. CONCLUSIONS: The nomogram accurately identified CP/CPPS patients who would benefit from acupuncture. Factors such as youth, abstention from alcohol, avoiding sedentary habits and staying up late, having high expectations for acupuncture, being free from comorbidities, and baseline high scores on both the NIH-CPSI pain subscale and total scores may positively affect the efficacy of acupuncture. Further validation of our findings requires multicenter and large-sample prospective studies.

A rapid on-site visualization platform based on RPA coupled with CRISPR-Cas12a for the detection of genetically modified papaya 'Huanong No.1'.

The Papaya ringspot virus (PRSV)-resistant genetically modified (GM) papaya 'Huanong No.1' has been certified as safe for consumption and widely planted in China for about 18 years. To protect consumers' rights and facilitate government supervision and monitoring, it is necessary to establish a simple, rapid, and specific detection method for 'Huanong No.1'. Herein, we developed a platform based on recombinase polymerase amplification (RPA) coupled with CRISPR-Cas12a for the detection of 'Huanong No.1'. The RPA-CRISPR-Cas12a platform was found to have high specificity, with amplification signals only present in 'Huanong No.1'. Additionally, the platform was highly sensitive, with a limit of detection (LOD) of approximately 20 copies. The detection process was fast and could be completed in less than 1 h. This novel platform enables the rapid on-site visualization detection of 'Huanong No.1', eliminating dependence on laboratory conditions and specialized instruments, and can serve as a technical reference for the rapid detection of other GM plants.

Subcutaneously transplanted xenogeneic protein recruits treg cells and M2 macrophages to induce browning of inguinal white adipose tissue.

OBJECTIVE: To study whether subcutaneously embedding xenogeneic protein threads or synthetic polymer absorbable threads can improve obesity phenotypes and metabolic conditions, and to further explore its underlying mechanism. METHODS: Thirty-six 8-week-old ob/ob mice were randomly allocated to three groups, respectively, receiving catgut embedding, PGA thread embedding or sham treatment bilaterally to the groin. Individual parameters including weight, food intake, and core temperature are recorded and metabolism assessment, energy expenditure analysis, and PET/CT scanning are also performed at fixed timepoints. After surgical incision, the inguinal white adipose tissue was histologically examined and its expression profile was tested and compared among groups 4 weeks and 12 weeks after operation. RESULTS: Catgut embedding reduced weight gain and improved metabolic status in ob/ob mice. Browning of bilateral inguinal WAT (white adipose tissue) was induced after catgut embedding, with massive infiltration of Treg cells and M2 macrophages in the tissue slices of fat pads. IL-10 and TGF-ß released by Treg cells targeted macrophages and the induced M2 macrophages increased the expression of thermogenic and anti-inflammatory genes in fat. The secretion of catecholamines by polarized M2 macrophages led to the activation of ß3-AR-related pathways in adipocytes and the browning of adipose tissue. CONCLUSIONS: Abdominal subcutaneous catgut embedding has the potential to combat obesity through the induction of WAT browning mediated by infiltrated Treg cells and macrophages.

Durable Effect of Acupuncture for Chronic Neck Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: Chronic neck pain, a prevalent health concern characterized by frequent recurrence, requires exploration of treatment modalities that provide sustained relief. This systematic review and meta-analysis aimed to evaluate the durable effects of acupuncture on chronic neck pain. METHODS: We conducted a literature search up to March 2024 in six databases, including PubMed, Embase, and the Cochrane Library, encompassing both English and Chinese language publications. The main focus of evaluation included pain severity, functional disability, and quality of life, assessed at least 3 months post-acupuncture treatment. The risk of bias assessment was conducted using the Cochrane Risk of Bias 2.0 tool, and meta-analyses were performed where applicable. RESULTS: Eighteen randomized controlled trials were included in the analysis. Acupuncture as an adjunct therapy could provide sustained pain relief at three (SMD: - 0.79; 95% CI - 1.13 to - 0.46; p < 0.01) and six (MD: - 18.13; 95% CI - 30.18 to - 6.07; p < 0.01) months post-treatment. Compared to sham acupuncture, acupuncture did not show a statistically significant difference in pain alleviation (MD: - 0.12; 95% CI - 0.06 to 0.36; p = 0.63). However, it significantly improved functional outcomes as evidenced by Northwick Park Neck Pain Questionnaire scores 3 months post-treatment (MD: - 6.06; 95% CI - 8.20 to - 3.92; p < 0.01). Although nine studies reported an 8.5%-13.8% probability of adverse events, these were mild and transitory adverse events. CONCLUSION: Acupuncture as an adjunct therapy may provide post-treatment pain relief lasting at least 3 months for patients with chronic neck pain, although it is not superior to sham acupuncture, shows sustained efficacy in improving functional impairment for over 3 months, with a good safety profile.

Nucleic Acid Sensor-Mediated PANoptosis in Viral Infection.

Innate immunity, the first line of host defense against viral infections, recognizes viral components through different pattern-recognition receptors. Nucleic acids derived from viruses are mainly recognized by Toll-like receptors, nucleotide-binding domain leucine-rich repeat-containing receptors, absent in melanoma 2-like receptors, and cytosolic DNA sensors (e.g., Z-DNA-binding protein 1 and cyclic GMP-AMP synthase). Different types of nucleic acid sensors can recognize specific viruses due to their unique structures. PANoptosis is a unique form of inflammatory cell death pathway that is triggered by innate immune sensors and driven by caspases and receptor-interacting serine/threonine kinases through PANoptosome complexes. Nucleic acid sensors (e.g., Z-DNA-binding protein 1 and absent in melanoma 2) not only detect viruses, but also mediate PANoptosis through providing scaffold for the assembly of PANoptosomes. This review summarizes the structures of different nucleic acid sensors, discusses their roles in viral infections by driving PANoptosis, and highlights the crosstalk between different nucleic acid sensors. It also underscores the promising prospect of manipulating nucleic acid sensors as a therapeutic approach for viral infections.

Discovery of Novel Non-Nucleoside Inhibitors Interacting with Dizinc Ions of CD73.

High extracellular concentrations of adenosine triphosphate (ATP) in the tumor microenvironment generate adenosine by sequential dephosphorylation of CD39 and CD73, resulting in potent immunosuppression to inhibit T cell and natural killer (NK) cell function. CD73, as the determining enzyme for adenosine production, has been shown to correlate with poor clinical tumor prognosis. Conventional inhibitors as analogues of adenosine 5'-monophosphate (AMP) may have a risk of further metabolism to adenosine analogues. Here, we report a new series of malonic acid non-nucleoside inhibitors coordinating with zinc ions of CD73. Compound 12f was found to be a superior CD73 inhibitor (IC50 = 60 nM) by structural optimization, and its pharmacokinetic properties were investigated. In mouse tumor models, compound 12f showed excellent efficacy and reversal of immunosuppression in combination with chemotherapeutic agents or checkpoint inhibitors, suggesting that it deserves further development as a novel CD73 inhibitor.

Seroprevalence of the novel swine acute diarrhea syndrome coronavirus in China assessed by enzyme-linked immunosorbent assay.

The endemic outbreak of SADS-CoV has resulted in economic losses and potentially threatened the safety of China's pig industry. The molecular epidemiology of SADS-CoV in pig herds has been investigated in many provinces in China. However, there are no data over a long-time span, and there is a lack of extensive serological surveys to assess the prevalence of SADS-CoV in Chinese swine herds since the discovery of SADS-CoV. In this study, an indirect anti-SADS-CoV IgG enzyme-linked immunosorbent assay (ELISA) based on the SADS-CoV S1 protein was established to investigate the seroprevalence of SADS-CoV in Chinese swine herds. Cross-reactivity assays, indirect immunofluorescence, and western blotting assays showed that the developed ELISA had excellent SADS-CoV specificity. In total, 12,978 pig serum samples from 29 provinces/municipalities/autonomous regions in China were tested from 2022 to 2023. The results showed that the general seroprevalence of SADS-CoV in China was 59.97%, with seroprevalence ranging from 16.7% to 77.12% in different provinces and from 42.61% to 68.45% in different months. SADS-CoV is widely prevalent in China, and its seroprevalence was higher in Northeast China, North China, and Central China than in other regions. Among the four seasons, the prevalence of SADS-CoV was the highest in spring and the lowest in autumn. The results of this study provide the general seroprevalence profile of SADS-CoV in China, facilitating the understanding of the prevalence of SADS-CoV in pigs. More importantly, this study is beneficial in formulating preventive and control measures for SADS-CoV and may provide directions for vaccine development.

Droplet Energy Harvesting System Based on Total-Current Nanogenerator.

The droplet-based nanogenerator (DNG) is a highly promising technology for harvesting high-entropy water energy in the era of the Internet of Things. Yet, despite the exciting progress made in recent years, challenges have emerged unexpectedly for the AC-type DNG-based energy system as it transitions from laboratory demonstrations to real-world applications. In this work, we propose a high-performance DNG system based on the total-current nanogenerator concept to address these challenges. This system utilizes the water-charge-shuttle architecture for easy scale-up, employs the field effect to boost charge density of the triboelectric layer, adopts an on-solar-panel design to improve compatibility with solar energy, and is equipped with a novel DC-DC buck converter as power management circuit. These features allow the proposed system to overcome the existing bottlenecks of DNG and empower the system with superior performances compared with previous ones. Notably, with the core architecture measuring only 15 cm × 12.5 cm × 0.3 cm in physical dimensions, this system reaches a record-high open-circuit voltage of 4200 V, capable of illuminating 1440 LEDs, and can charge a 4.7 mF capacitor to 4.5 V in less than 24 min. In addition, the practical potential of the proposed DNG system is further demonstrated through a self-powered, smart greenhouse application scenario. These demonstrations include the continuous operation of a thermohygrometer, the operation of a Bluetooth plant monitor, and the all-weather energy harvesting capability. This work will provide valuable inspiration and guidance for the systematic design of next-generation DNG to unlock the sustainable potential of distributed water energy for real-world applications.

Effects of electroacupuncture on chronic urinary retention after pelvic or lumbosacral tumor resection surgeries: a retrospective cohort study.

Background: Chronic urinary retention (CUR) resulting from lower motor neuron lesions (LMNL) is a medical condition secondary to pelvic or lumbosacral tumor resection surgeries. Electroacupuncture (EA) is proved to be effective and safe in treating certain lower urinary tract disorders. However, the clinical benefit and optimal duration of EA treatment for CUR following LMNL remain unknown. Methods: Using a retrospective cohort design, 20 eligible patients diagnosed with CUR resulting from LMNL secondary to pelvic or lumbosacral tumor resection surgeries were included from March 1, 2017, to June 30, 2020. The patients were treated by EA three times a week for 2 to 12 weeks and followed up for 24 weeks after treatment. The electric stimulators with a 5-Hz continuous wave (5-10 mA intensity) were separately connected to bilateral Ciliao (BL32), bilateral Zhongliao (BL33), and bilateral Huiyang (BL35), and stimulators with a 10-Hz continuous wave (1-2 mA intensity) were connected to bilateral Sanyinjiao (SP6). Current intensity was adjusted according to the patients' individual tolerance. The median follow-up was 32 weeks (range, 26-36 weeks). Responders were defined as patients whose post-void residuals (PVR) reduced by 50% or more from baseline. Adverse event was recorded. Results: Totally 20 patients [mean (standard deviation) age, 48.1 (15.5) years; 9 men (45.0%); 11 women (55.0%)] were included. Of the 20 patients, 14 (70.0%) had responded to EA treatment and stopped catheterization for achieving satisfactory spontaneous urination (PVR <100 mL without complications), 7 (35.0%) had complete resolution (90-100% reduction in PVR from baseline), and 13 (65.0%) scored 1 (much better) or 2 (moderately better) in the Patient Global Impression of Improvement (PGI-I) assessment. Moreover, 6 (30.0%) patients had responded within 4 weeks of EA treatment. According to Kaplan-Meier survival curve, we found that more than 50% patients could respond to EA treatment within 8 weeks or longer. None of the responders had ever experienced relapse in 24 weeks after EA treatment ended. None of the patients manifested urinary tract infection (UTI), newly diagnosed hydroureter or hydronephrosis. One patient diagnosed with hydronephrosis at baseline recovered after 12-week EA treatment. Two patients with UTI at baseline were prescribed antibiotics and did not present UTI again during the follow-up. Conclusions: EA could be a promising treatment option for CUR caused by LMNL following pelvic or lumbosacral tumor resection surgeries, with long-term effects and a good safety profile. The optimal duration of EA should be of 8 weeks at least. But this was a retrospective cohort study of a small sample size, so future studies are needed to investigate EA in larger populations in randomized controlled trials.

Genome-wide association study and genomic prediction for resistance to brown planthopper in rice.

The brown planthopper (BPH) is the most destructive insect pest that threatens rice production globally. Developing rice varieties incorporating BPH-resistant genes has proven to be an effective control measure against BPH. In this study, we assessed the resistance of a core collection consisting of 502 rice germplasms by evaluating resistance scores, weight gain rates and honeydew excretions. A total of 117 rice varieties (23.31%) exhibited resistance to BPH. Genome-wide association studies (GWAS) were performed on both the entire panel of 502 rice varieties and its subspecies, and 6 loci were significantly associated with resistance scores (P value < 1.0e-8). Within these loci, we identified eight candidate genes encoding receptor-like protein kinase (RLK), nucleotide-binding and leucine-rich repeat (NB-LRR), or LRR proteins. Two loci had not been detected in previous study and were entirely novel. Furthermore, we evaluated the predictive ability of genomic selection for resistance to BPH. The results revealed that the highest prediction accuracy for BPH resistance reached 0.633. As expected, the prediction accuracy increased progressively with an increasing number of SNPs, and a total of 6.7K SNPs displayed comparable accuracy to 268K SNPs. Among various statistical models tested, the random forest model exhibited superior predictive accuracy. Moreover, increasing the size of training population improved prediction accuracy; however, there was no significant difference in prediction accuracy between a training population size of 737 and 1179. Additionally, when there existed close genetic relatedness between the training and validation populations, higher prediction accuracies were observed compared to scenarios when they were genetically distant. These findings provide valuable resistance candidate genes and germplasm resources and are crucial for the application of genomic selection for breeding durable BPH-resistant rice varieties.

Injectable platelet-rich fibrin promotes proliferation and trichogenic inductivity of dermal papilla cells through activating TGF-ß/Smad signaling pathway.

Dermal papilla cell (DPC) belongs to a specialized mesenchymal stem cell for hair follicle regeneration. Maintaining the ability of DPCs to stimulate hair in vitro culture is important for hair follicle morphogenesis and regeneration. As the third generation of platelet concentrate, injectable platelet-rich fibrin (i-PRF) is a novel biomaterial containing many growth factors and showing promising effects on tissue reconstruction. We aimed to explore the influences of i-PRF on the proliferative, migratory, as well as trichogenic ability of DPCs and compared the effects of i-PRF and platelet-rich plasma (PRP), the first generation of platelet concentrate. Both PRP and i-PRF facilitated DPCs proliferation, and migration, along with trichogenic inductivity as well as stimulated the TGF-ß/Smad pathway, while the impacts of i-PRF were more significant than PRP. A small molecule inhibitor of TGF-beta receptor I, Galunisertib, was also applied to treat DPCs, and it rescued the impacts of i-PRF on the proliferative, migratory, trichogenic inductivity, and proteins-associated with TGF-ß/Smad pathway in DPCs. These findings revealed that i-PRF had better effects than PRP in enhancing the proliferative, migratory, and hair-inducing abilities of DPCs by the TGF-ß/Smad pathway, which indicated the beneficial role of i-PRF in hair follicle regeneration.

Intellectual landscapes and emerging trends of non-steroidal mineralocorticoid receptor antagonists: a bibliometric and visual analysis.

PURPOSE: With increasing studies, non-steroidal mineralocorticoid receptor (MR) antagonists have been increasingly recognized as a major novel dimension in cardiorenal disease therapy. This bibliometric analysis aimed to uncover current research status and identify future research directions in the study of non-steroidal MR antagonists to inform subsequent investigations. METHODS: Relevant English-language literature was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection on January 10, 2024. Analyses of countries, institutions, authors, journals, documents, cited references and keywords were performed by the CiteSpace and VOSviewer software. RESULTS: Overall, 498 documents, including 297 articles and 201 reviews, were included and analyzed. The United States (n = 188), Bayer AG (n = 78), and Professor Peter Kolkhof (n = 59) were the most prolific country, institution, and author in this field, respectively. Cluster analysis of cited references identified major clusters like cardiovascular disease, chronic kidney disease, and omecamtiv mecarbil. Keyword analysis indicated that sodium-glucose transport protein (SGLT)-2 inhibitors, pharmacotherapy, clinical trial, and guideline have emerged recently. CONCLUSION: The field of non-steroidal MR antagonists is gradually gaining momentum as a novel pharmacotherapy in cardiorenal diseases, especially diabetic kidney disease, hypertension, and heart failure. Future studies will focus on add-on pharmacotherapy by combining non-steroidal MR antagonists with SGLT-2 inhibitors and the development and publication of clinical guidelines to facilitate patient management.

Discovery of a novel SHP2 allosteric inhibitor using virtual screening, FMO calculation, and molecular dynamic simulation.

CONTEXT: SHP2 is a non-receptor protein tyrosine phosphatase to remove tyrosine phosphorylation. Functionally, SHP2 is an essential bridge to connect numerous oncogenic cell-signaling cascades including RAS-ERK, PI3K-AKT, JAK-STAT, and PD-1/PD-L1 pathways. This study aims to discover novel and potent SHP2 inhibitors using a hierarchical structure-based virtual screening strategy that combines molecular docking and the fragment molecular orbital method (FMO) for calculating binding affinity (referred to as the Dock-FMO protocol). For the SHP2 target, the FMO method prediction has a high correlation between the binding affinity of the protein-ligand interaction and experimental values (R2 = 0.55), demonstrating a significant advantage over the MM/PBSA (R2 = 0.02) and MM/GBSA (R2 = 0.15) methods. Therefore, we employed Dock-FMO virtual screening of ChemDiv database of ∼2,990,000 compounds to identify a novel SHP2 allosteric inhibitor bearing hydroxyimino acetamide scaffold. Experimental validation demonstrated that the new compound (E)-2-(hydroxyimino)-2-phenyl-N-(piperidin-4-ylmethyl)acetamide (7188-0011) effectively inhibited SHP2 in a dose-dependent manner. Molecular dynamics (MD) simulation analysis revealed the binding stability of compound 7188-0011 and the SHP2 protein, along with the key interacting residues in the allosteric binding site. Overall, our work has identified a novel and promising allosteric inhibitor that targets SHP2, providing a new starting point for further optimization to develop more potent inhibitors. METHODS: All the molecular docking studies were employed to identify potential leads with Maestro v10.1. The protein-ligand binding affinities of potential leads were further predicted by FMO calculations at MP2/6-31G* level using GAMESS v2020 system. MD simulations were carried out with AmberTools18 by applying the FF14SB force field. MD trajectories were analyzed using VMD v1.9.3. MM/GB(PB)SA binding free energy analysis was carried out with the mmpbsa.py tool of AmberTools18. The docking and MD simulation results were visualized through PyMOL v2.5.0.

Factors related to acupuncture response in patients with chronic prostatitis/chronic pelvic pain syndrome: secondary analysis of a randomized controlled trial.

PURPOSE: Acupuncture has been recommended as an effective therapy to improve symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We conducted this secondary analysis to explore the factors that may influence the response of patients with CP/CPPS to acupuncture. METHODS: This secondary analysis was based on a randomized controlled trial demonstrating the efficacy of acupuncture among patients with CP/CPPS. Responder is defined as a patient with a decrease of ≥ 6 points in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score from baseline at the 32 week. 206 patients who received acupuncture treatment and completed 32-week follow-up were included in this secondary analysis. Descriptive statistics were used to describe the demographic and clinical characteristics of both responders and non-responders in acupuncture group. Logistic regression analysis with bootstrapping was made to identify potential factors that contributed to the effectiveness of acupuncture for treating CP/CPPS. Responders and non-responders were listed as dependent variables. RESULTS: In this study, 130 (63.11%) patients were assessed as responders. The results showed that men with non-sedentariness (OR 4.170 [95%CI 1.837 to 9.463; P = 0.001]), non-smoking habit (OR 2.824 [95%CI 1.453 to 5.487; P = 0.002]), without comorbidity (OR 8.788 [95%CI 1.912 to 40.295; P = 0.005]), and severe NIH-CPSI total score (OR 0.227 [95%CI 0.114 to 0.450; P < 0.0001]) benefited more from acupuncture intervention. CONCLUSION: CP/CPPS patients who are active, non-smokers, without comorbidity, and had severe symptoms may be more likely to respond to acupuncture.

Nonlinear error analysis of fast optical delay lines.

Optical delay lines have wide applications in terahertz time-domain spectroscopy and optical coherence tomography. In this study, a fast-rotating optical delay line (FRODL) with 24 turntable reflection surfaces was designed. By analyzing the working principle of the FRODL, a mathematical model was established for the nonlinear parameter error of the FRODL delay time. By constructing the polarization Michelson interference system and testing the FRODL structure, the error of actual assembly parameters of the FRODL was approximately 0.015 mm, the actual delay time of the FRODL was greater than 43.5 ps, and the linearity was 99.785%.

Traditional Chinese Medicine formula Dai-Zong-Fang alleviating hepatic steatosis in db/db mice via gut microbiota modulation.

Introduction: Hepatic steatosis is a hepatic pathological change closely associated with metabolic disorders, commonly observed in various metabolic diseases such as metabolic syndrome (MetS), with a high global prevalence. Dai-Zong-Fang (DZF), a traditional Chinese herbal formula, is widely used in clinical treatment for MetS, exhibiting multifaceted effects in reducing obesity and regulating blood glucose and lipids. This study aims to explore the mechanism by which DZF modulates the gut microbiota and reduces hepatic steatosis based on the gut-liver axis. Methods: This study utilized db/db mice as a disease model for drug intervention. Body weight and fasting blood glucose were monitored. Serum lipid and transaminase levels were measured. Insulin tolerance test was conducted to assess insulin sensitivity. Hematoxylin and eosin (HE) staining was employed to observe morphological changes in the liver and intestine. The degree of hepatic steatosis was evaluated through Oil Red O staining and hepatic lipid determination. Changes in gut microbiota were assessed using 16S rRNA gene sequencing. Serum lipopolysaccharide (LPS) levels were measured by ELISA. The expression levels of intestinal tight junction proteins, intestinal lipid absorption-related proteins, and key proteins in hepatic lipid metabolism were examined through Western blot and RT-qPCR. Results: After DZF intervention, there was a decrease in body weight, alleviation of glucose and lipid metabolism disorders, reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and mitigation of insulin resistance in mice. DZF significantly modulated the diversity of the gut microbiota, with a notable increase in the abundance of the Bacteroidetes phylum. PICRUSt indicated that DZF influenced various functions in gut microbiota, including carbohydrate and amino acid metabolism. Following DZF intervention, serum LPS levels decreased, intestinal pathological damage was reduced, and the expression of intestinal tight junction protein occludin was increased, while the expression of intestinal lipid absorption-related proteins cluster of differentiation 36 (CD36) and apolipoprotein B48 (ApoB48) were decreased. In the liver, DZF intervention resulted in a reduction in hepatic steatosis and lipid droplets, accompanied by a decrease fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) and fatty acid transport protein 2 (FATP2). Conversely, there was an increase in the expression of the fatty acid oxidation-related enzyme carnitine palmitoyltransferase-1𝛂 (CPT-1𝛂). Conclusion: DZF can regulate the structure and function of the intestinal microbiota in db/db mice. This ameliorates intestinal barrier damage and the detrimental effects of endotoxemia on hepatic metabolism. DZF not only inhibits intestinal lipid absorption but also improves hepatic lipid metabolism from various aspects, including de novo lipogenesis, fatty acid uptake, and fatty acid oxidation. This suggests that DZF may act on the liver and intestine as target organs, exerting its effects by improving the intestinal microbiota and related barrier and lipid absorption functions, ultimately ameliorating hepatic steatosis and enhancing overall glucose and lipid metabolism.