SMYD2 induced PGC1α methylation promotes stemness maintenance of glioblastoma stem cells.

BACKGROUND: The high fatality rate of glioblastoma (GBM) is attributed to glioblastoma stem cells (GSCs), which exhibit heterogeneity and therapeutic resistance. Metabolic plasticity of mitochondria is the hallmark of GSCs. Targeting mitochondrial biogenesis of GSCs is crucial for improving clinical prognosis in GBM patients. METHODS: SMYD2-induced PGC1α methylation and followed nuclear export is confirmed by co-immunoprecipitation, cellular fractionation, and immunofluorescence. The effects of SMYD2/PGC1α/CRM1 axis on GSCs mitochondrial biogenesis is validated by OCR, ECAR and intracranial glioma model. RESULTS: PGC1α methylation causes disabled mitochondrial function to maintain the stemness, thereby enhancing radio-resistance of GSCs. SMYD2 drives PGC1α K224 methylation (K224me), which is essential for promoting the stem-like characteristics of GSCs. PGC1α K224me is preferred binding with CRM1, accelerating PGC1α nuclear export and subsequent dysfunction. Targeting PGC1α methylation exhibits significant radiotherapeutic efficacy and prolongs patient survival. CONCLUSIONS: These findings unveil a novel regulatory pathway involving mitochondria that governs stemness in GSCs, thereby emphasizing promising therapeutic strategies targeting PGC1α and mitochondria for the treatment of GBM.

Influences of Cluster Thinning on Fatty Acids and Green Leaf Volatiles in the Production of Cabernet Sauvignon Grapes and Wines in the Northwest of China.

Cluster thinning has been widely applied in yield management and its effect on green leaf volatiles (GLVs) in wines has seldom been studied. GLVs are important flavor compositions for grapes and wines. This work aimed to investigate the impact of cluster thinning on these volatiles and their precursors in grapes and wines. Severe cluster thinning (CT1) and medium cluster thinning (CT2) were performed on Cabernet Sauvignon (Vitis vinifera L.) vines in two sites (G-farm and Y-farm) from Xinjiang province in the Northwest of China. The impact of cluster thinning treatments on the accumulation of GLVs and their precursors, long chain fatty acids (LCFAs) of grape berries and C6 volatiles, in resulting wines was investigated. Multivariate analysis showed that cluster thinning treatments induced significant changes in fruit and wine composition in both farms. In Y-farm, medium cluster thinning (CT2) significantly increased the average cluster weight of harvested berries. Additionally, both cluster thinning treatments (CT1 and CT2) increased fatty acids in harvested berries and CT2 led to an increase in C6 esters and a decrease in C6 alcohols in the wines of Y-farm under the warmer and drier 2012 vintage. However, the effect of cluster thinning was likely negative in G-farm due to its wetter soil and excessive organic matter. The treatments may be applicable for local grape growers to improve viticultural practices for the more balanced vegetative and reproductive growth of Cabernet Sauvignon grapevines. This work also provided further knowledge on the regulation of fatty acids and the derived C6 volatiles through the lipoxygenase (LOX) pathway.

Prospect of value and application of transcutaneous electrical acupoint stimulation to control blood pressure in proactive healthcare perspective. / 主动健康视域下经皮穴位电刺激调控血压的价值与应用展望.

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.

IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME. IFI35 induced non-canonical NF-kB signaling through proteasomal processing of p105 to the DNA-binding transcription factor p50, which heterodimerizes with RELB (RELB/p50), and activated cell chemotaxis in a cell-autonomous manner. Further, IFI35 induced recruitment and maintenance of M2-like TAMs in TME in a paracrine manner. Targeting IFI35 effectively suppressed in vivo tumor growth and prolonged survival of orthotopic xenograft-bearing mice. Collectively, these findings reveal the tumor-promoting functions of IFI35 and suggest that targeting IFI35 or its downstream effectors may provide effective approaches to improve GBM treatment.

Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells. Isotope tracing coupled with mass spectrometry analysis confirmed that fumarate, generated by adenylosuccinate lyase (ADSL) in the de novo purine synthesis pathway that is highly activated in GSCs, promoted PTEN C211 succination. This modification abrogated the interaction between PTEN and MMS19, reactivating the CIA machinery pathway in GSCs. Functionally, inhibiting PTEN C211 succination by reexpressing a PTEN C211S mutant, depleting ADSL by shRNAs, or consuming fumarate by the US Food and Drug Administration-approved prescription drug N-acetylcysteine (NAC) impaired GSC maintenance. Reexpressing PTEN C211S or treating with NAC sensitized GSC-derived brain tumors to temozolomide and irradiation, the standard-of-care treatments for patients with glioblastoma, by slowing CIA machinery-mediated DNA damage repair. These findings reveal an immediately practicable strategy to target GSCs to treat glioblastoma by combination therapy with repurposed NAC.

Cabrol procedure and its modifications: a systematic review and meta-analysis.

BACKGROUND: The Cabrol procedure has undergone various modifications and developments since its invention. However, there is a notable gap in the literature regarding meta-analyses assessing it. METHODS: A systematic review and meta-analysis was conducted to evaluate the effectiveness and long-term outcomes of the Cabrol procedure and its modifications. Pooling was conducted using random effects model. Outcome events were reported as linearized occurrence rates (percentage per patient-year) with 95% confidence intervals. RESULTS: A total of 14 studies involving 833 patients (mean age: 50.8 years; 68.0% male) were included in this meta-analysis. The pooled all-cause early mortality was 9.0% (66 patients), and the combined rate of reoperation due to bleeding was 4.9% (17 patients). During the average 4.4-year follow-up (3,727.3 patient-years), the annual occurrence rates (linearized) for complications were as follows: 3.63% (2.79-4.73) for late mortality, 0.64% (0.35-1.16) for aortic root reoperation, 0.57% (0.25-1.31) for hemorrhage events, 0.66% (0.16-2.74) for thromboembolism, 0.60% (0.29-1.26) for endocarditis, 2.32% (1.04-5.16) for major valve-related adverse events, and 0.58% (0.34-1.00) for Cabrol-related coronary graft complications. CONCLUSION: This systematic review provides evidence that the outcomes of the Cabrol procedure and its modifications are acceptable in terms of mortality, reoperation, anticoagulation, and valve-related complications, especially in Cabrol-related coronary graft complications. Notably, the majority of Cabrol procedures were performed in reoperations and complex cases. Furthermore, the design and anastomosis of the Dacron interposition graft for coronary reimplantation, considering natural anatomy and physiological hemodynamics, may promise future advancements in this field.

Inhibitory Impact Of Cinobufagin In Triple-Negative Breast Cancer Metastasis: Involvements Of Macrophage Reprogramming Through Upregulated MME and Inactivated FAK/STAT3 Signaling.

BACKGROUND: Cinobufagin (CBG), a key bioactive component in cinobufacini, exhibits antitumor properties. This study explores CBG's impact on triple-negative breast cancer (TNBC) metastasis and elucidates the underpinning mechanism. METHODS: Murine xenograft and orthotopic metastatic TNBC models were generated and treated with CBG. The burden of metastatic tumor in the mouse lung, the epithelial to mesenchymal transition (EMT) markers, and macrophage polarization markers within the tumors were examined. The phenotype of tumor-associated macrophages (TAMs) and mobility of TNBCs in vitro in a macrophage-TNBC cell coculture system were analyzed. Physiological targets of CBG were identified by bioinformatics analyses. RESULTS: CBG treatment significantly alleviated lung tumor burden and EMT activity. It triggered an M2-to-M1 shift in TAMs, resulting in decreased TNBC cell migration, invasion, and EMT in vitro. CBG upregulated membrane metalloendopeptidase (MME) expression, suppressing FAK and STAT3 phosphorylation. Silencing of MME, either in mice or TAMs, counteracted CBG effects, reinstating M2 TAM predominance and enhancing TNBC cell metastasis. Cotreatment with Defactinib, a FAK antagonist, reversed M2 TAM polarization and TNBC cell metastasis. Notably, MME silencing in TNBC cells had no impact on CBG-suppressed malignant properties, indicating MME's indirect involvement in TNBC cell behavior through TAM mediation. CONCLUSION: This study unveils CBG's ability to enhance MME expression, deactivate FAK/STAT3 signaling, and inhibit TNBC metastasis by suppressing M2-skewed macrophages.

Enhancing dendrobine production in Dendrobium nobile through mono-culturing of endophytic fungi, Trichoderma longibrachiatum (MD33) in a temporary immersion bioreactor system.

Introduction: Dendrobine, a valuable alkaloid found in Dendrobium nobile, possesses significant pharmaceutical potential. Methods: In this study, we explored innovative approaches to enhance dendrobine production by utilizing endophytic fungi in a Temporary Immersion Bioreactor System (TIBS, Nanjing BioFunction Co. Ltd., China) and traditional test bottles. Dendrobine was unequivocally identified and characterised in D. nobile co-culture seedlings through UHPLC analysis and LC-MS qTOF analysis, supported by reference standards. Results: The CGTB (control group) and EGTB (experimental group) 12-month-old D. nobile seedlings exhibited similar peak retention times at 7.6±0.1 minutes, with dendrobine identified as C16H25NO2 (molecular weight 264.195). The EGTB, co-cultured with Trichoderma longibrachiatum (MD33), displayed a 2.6-fold dendrobine increase (1804.23 ng/ml) compared to the CGTB (685.95 ng/ml). Furthermore, a bioanalytical approach was applied to investigate the mono-culture of T. longibrachiatum MD33 with or without D. nobile seedlings in test bottles. The newly developed UHPLC-MS method allowed for dendrobine identification at a retention time of 7.6±0.1 minutes for control and 7.6±0.1 minutes for co-culture. Additionally, we explored TIBS to enhance dendrobine production. Co-culturing D. nobile seedlings with Trichoderma longibrachiatum (MD33) in the TIBS system led to a substantial 9.7-fold dendrobine increase (4415.77 ng/ml) compared to the control (454.01 ng/ml) after just 7 days. The comparative analysis of dendrobine concentration between EGTB and EGTIBS highlighted the remarkable potential of TIBS for optimizing dendrobine production. Future research may focus on scaling up the TIBS approach for commercial dendrobine production and investigating the underlying mechanisms for enhanced dendrobine biosynthesis in D. nobile. The structural elucidation of dendrobine was achieved through 1H and 13C NMR spectroscopy, revealing a complex array of proton environments and distinct carbon environments, providing essential insights for the comprehensive characterization of the compound. Discussion: These findings hold promise for pharmaceutical and industrial applications of dendrobine and underline the role of endophytic fungi in enhancing secondary metabolite production in medicinal plants.

Transcriptomic profiling of adding cobalt chloride to improve dendrobine-type total alkaloid production.

Trichoderma longibrachiatum UN32 is known for its efficient production of dendrobine-type total alkaloids (DTTAs). This study aimed to determine the optimal medium composition for the UN32 strain using response surface methodology. Key factors, including glucose, beef extract, and CoCl2, were selected through the Plackett-Burman design. Subsequently, a factorial optimization approach was employed using the steepest ascent design, and 17 trial sets were completed via the Box-Behnken design. The optimal medium composition was found to consist of 29.4 g/L of glucose, 17.3 g/L of beef extract, and 0.28 mmol/L of CoCl2. This optimized medium resulted in an impressive 80.8% increase in mycelial dry weight (reaching 12.303 g/L) and a substantial 76.4% boost in DTTA production (reaching 541.63 ± 46.95 µg). Furthermore, the fermentation process was scaled up to a 5-L bioreactor, leading to a DTTA production approximately 1.95 times than the control. Transcriptome analysis of strain UN32 in response to CoCl2 supplementation revealed significant changes in the expression of critical genes associated with the TCA cycle and L-valine, L-leucine, and L-isoleucine biosynthesis changed. These alterations resulted in a heightened influx of acetyl-CoA into DTTA production. Additionally, the expression of genes related to antioxidant enzymes was modified to maintain homeostasis of reactive oxygen species (ROS). A potential mechanism for the accumulation of DTTAs based on ROS as a signal transduction was proposed. These findings provide valuable insights into the regulatory mechanisms of DTTA biosynthesis, potentially offering a method to enhance the production of secondary metabolites in the UN32 strain. KEY POINTS: • After the RSM optimization, there is a substantial increase of 80.8% in biomass production and a significant 76.4% rise in DTTA production. • Transcriptome analysis revealed that the inclusion of CoCl2 supplements resulted in an enhanced influx of acetyl-CoA. • Proposed a mechanism for the accumulation of DTTAs for the role of ROS as a signal transduction pathway.

Circulating lung cancer biomarkers: From translational research to clinical practice.

Fundamental studies on biomarkers as well as developed assays for their detection can provide valuable information facilitating clinical decisions. For patients with lung cancer, there are established circulating biomarkers such as serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and cytokeratin-19 fragment (CYFRA21-1). There are also molecular biomarkers for targeted therapy such as epidermal growth factor receptor (EGFR) gene, anaplastic lymphoma kinase (ALK) gene, KRAS gene, and BRAF gene. However, there is still an unmet need for biomarkers that can be used for early detection and predict treatment response and survival. In this review, we describe the lung cancer biomarkers that are currently being used in clinical practice. We also discuss emerging preclinical and clinical studies on new biomarkers such as omics-based biomarkers for their potential clinical use to detect, predict, or monitor subtypes of lung cancer. Additionally, between-method differences in tumor markers warrant further development and improvement of the standardization and harmonization for each assay.

Perspective of Calcium Imaging Technology Applied to Acupuncture Research / 中国结合医学杂志

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.

Prevention and Treatment of Lung Cancer by Traditional Chinese Medicine Targeting Wnt/β-catenin Signaling Pathway： A Review / 中国实验方剂学杂志

Lung cancer is one of the most common malignant tumors in the world， with its morbidity and mortality ranking at the top. The early symptoms are not obvious， and the biological structure is complex， so many patients have missed the optimal treatment time. At present， the treatment of lung cancer in modern medicine is dominated by first-line chemotherapy and surgical treatment with platinum-containing regimen， which has relatively large side effects， poor prognosis， and a high risk of metastasis and recurrence. With the gradual rise of targeted therapy and immunotherapy for lung cancer， the overall recovery of patients with lung cancer is still poor and the survival rate is low， despite more abundant treatment methods. From the perspective of holistic concept and syndrome differentiation， traditional Chinese medicine （TCM） plays an important role in the prognosis of tumor patients， with many targets， a wide range and light toxic and side effect. Modern studies have shown that the occurrence and development of lung cancer are closely related to the abnormality of multiple signaling pathways， and the Wnt/β-catenin signaling pathway， as one of the most important pathways in cancer， is involved in the whole process of lung cancer development by regulating the expression of related signaling proteins and genes. In recent years， many studies have confirmed that TCM monomers and TCM compounds can inhibit the epithelial-mesenchymal transition （EMT） process of lung cancer and the activity of lung cancer stem cells （LCSCs） by regulating the Wnt/β-catenin signaling pathway， induce lung cancer cell apoptosis， inhibit the proliferation， invasion and migration of lung cancer cells， and thus play an anti-lung cancer role. In recent years， research in this field has made breakthroughs， but there is a lack of systematic reviews and summaries. Thus， this paper reviewed relevant literature worldwide to analyze and interpret the mechanism of TCM intervention in the Wnt/β-catenin signaling pathway against lung cancer. The TCM monomers targeted to regulate this signaling pathway were summarized in four categories： promoting blood circulation for removing blood stasis， clearing heat and removing dampness， clearing heat and removing toxicity， and awakening the spirit. TCM compounds included Buzhong Yiqitang， Xuefu Zhuyutang， et al. This study aims to provide new ideas for clinical research and drug development for lung cancer.

Clinical characteristics and treatment analysis of three cases of congenital ulnar collateral flexor contracture of the forearm / 中国修复重建外科杂志

OBJECTIVE@#To report the clinical characteristics and treatment analysis of 3 cases of congenital ulnar collateral flexor contracture of the forearm and take a reference for clinic.@*METHODS@#A total of 3 patients with congenital ulnar collateral flexor contracture of the forearm were admitted between February 2019 and August 2021. Two patients were male and 1 was female, and their ages were 16, 20, and 16 years, respectively. The disease durations were 8, 20, and 15 years, respectively. They all presented with flexion deformity of the proximal and distal interphalangeal joints of the middle, ring, and little fingers in the neutral or extended wrist position, and the deformity worsened in the extended wrist position. The total action motion (TAM) scores of 3 patients were 1 and the gradings were poor. The Carroll's hand function evaluation scores were 48, 55, and 57, and the grip strength indexes were 72.8, 78.4, and 30.5. Preoperative CT of case 2 showed a bony protrusion of the flexor digitorum profundus tendon at the proximal end of the ulna; and MRI of case 3 showed that the ulnar flexor digitorum profundus presented as a uniform cord. After diagnosis, all patients were treated with operation to release the denatured tendon, and functional exercise was started early after operation.@*RESULTS@#The incisions of 3 patients healed by first intention. Three patients were followed up for 12, 35, and 12 months, respectively. The hand function and the movement range of the joints significantly improved, but the grip strength did not significantly improve. At last follow-up, TAM scores were 3, 4, and 4, respectively, among which 2 cases were excellent and 1 case was good. Carroll's hand function evaluation scores were 95, 90, and 94, and the grip strength indexes were 73.5, 81.3, and 34.2, respectively.@*CONCLUSION@#Congenital ulnar collateral flexor contracture is a rare clinical disease that should be distinguished from ischemic muscle contracture. The location of the contracture should be identified and appropriate surgical timing should be selected for surgical release. Active postoperative rehabilitation and functional exercise can achieve good hand function.

Decoding the aroma characteristics of icewine by partial least-squares regression, aroma reconstitution, and omission studies.

The appeal of icewine is attributable to its distinct aroma characteristics, such as 'honey', 'caramel', and 'dried fruit', but little is known about the chemical basis of these aroma attributes. A set of icewines with different aroma intensities were selected by a panel of wine experts. Detailed volatile compound analyses and sensory descriptive analyses were performed on the selected icewines. Using partial least-squares regression, several lactones, esters, terpenes, furanones, and ß-damascenone were positively correlated with 'honey', 'caramel', and 'dried fruit' aromas. Aroma reconstitution studies confirmed that terpenes could significantly enhance the 'honey' aroma, but weaken the 'caramel' aroma, while lactones and furanones could significantly enhance the 'caramel' and 'dried fruit' aromas. In addition, this study demonstrated that terpenes, lactones, and furanones interacted synergistically with each other to cause the sensory perception of the characteristic aromas of icewine.

Fluoxetine mitigates depressive-like behaviors in mice via anti-inflammation and enhancing neuroplasticity.

Neuroplasticity and inflammation represent a common final pathway for effective antidepressant treatment. SSRIs are the most commonly prescribed medications for depression and have demonstrated efficacy in reducing depressive symptoms. However, the precise impact of SSRIs on neuroplasticity and inflammation remains unclear. In this study, we aimed to investigate the influence of long-term treatment with SSRIs on hippocampal neuron, inflammation, synaptic function and morphology. Our findings revealed that fluoxetine treatment significantly alleviated behavioral despair, anhedonia, and anxiety in reserpine-treated mice. Moreover, fluoxetine mitigated hippocampal neuron impairment, inhibited inflammatory release, and increased the expression of synaptic proteins markers (SYP and PSD95) in mice. Notably, fluoxetine also suppressed reserpine-induced synapse loss in the hippocampus. Based on these results, fluoxetine has been demonstrated effectively to ameliorate depressive mood and cognitive dysfunction, possibly through the enhancement of synaptic plasticity. Overall, our study contributes to a further understanding of the mechanisms underlying the therapeutic effects of fluoxetine and its potential role in improving depressive symptoms and cognitive impairments.

Effects of acupoints-based TENS combined with tDCS on spasticity and motor function in ischemic stroke with spastic hemiplegia: study protocol for a randomized controlled trial.

Background: Spastic hemiplegia following ischemic strokes seriously impedes the recovery of motor function posing a vast rehabilitation challenge. As the uncertain effects of recommended conventional treatments such as botulinum toxin injections on active functional improvement and potential adverse effects cannot be bypassed, there is an increasing need in alternative, more effective and safer modalities. Acupoints-based transcutaneous electrical nerve stimulation (Acu-TENS) and transcranial direct current stimulation (tDCS) are effective non-invasive modalities for stroke rehabilitation, particularly showing anti-spastic effect and functional improvements as well. However, the optimal stimulation frequency of Acu-TENS and whether combination of Acu-TENS and tDCS exert synergistic effect remain to be investigated. Objective: To evaluate the effects of Acu-TENS combined with tDCS on spasticity and motor function in ischemic stroke patients with spastic hemiplegia and screen the optimal frequency of Acu-TENS. Methods: A total of 90 post-ischemic stroke patients with spastic hemiplegia will be intervened for 4 weeks and followed up for 4 weeks. They will be randomly assigned to three groups including two observation groups and a standard care control group in a 1:1:1 ratio. All patients will receive standard care and regular rehabilitation accordingly. In addition, the two observation groups will receive 12 sessions of Acu-TENS at 20 Hz or 100 Hz for 30 min combined with 1 mA tDCS for 20 min, three times a week, for 4 weeks. The primary outcome is the change in total modified Ashworth scale (MAS) score from baseline to week 4. Secondary outcomes include changes in surface electromyography (SEMG), Fugl-Meyer Motor Function Scale, Modified Barthel Index (MBI), and 10-meter walk test from baseline to week 4. MAS score will also be measured after 4 weeks of follow-up. Adverse events throughout the study will be recorded. Discussion: This trial will evaluate, for the first time, the therapeutic potentials and safety of Acu-TENS combined with tDCS on spasticity and motor function in stroke patients. It will provide evidence for frequency-dependent anti-spastic effect of Acu-TENS, and a reference for rated parameter setting of new mixed transcutaneous and transcranial stimulation system for stroke rehabilitation, thereby promoting proactive healthcare consequently. Trial registration: Chinese Clinical Trials Register ChiCTR2200067186.

Building quality primary health care development in the new era towards universal health coverage: a Beijing initiative.

Primary health care (PHC) is the most effective way to improve people's health and well-being, and primary care services should act as the cornerstone of a resilient health system and the foundation of universal health coverage. To promote high quality development of PHC, an International Symposium on Quality Primary Health Care Development was held on December 4-5, 2023 in Beijing, China, and the participants have proposed and advocated the Beijing Initiative on Quality Primary Health Care Development. The Beijing Initiative calls on all countries to carry out and strengthen 11 actions: fulfill political commitment and accountability; achieve "health in all policies" through multisectoral coordination; establish sustainable financing; empower communities and individuals; provide community-based integrated care; promote the connection and integration of health services and social services through good governance; enhance training, allocation and motivation of health workforce, and medical education; expand application of traditional and alternative medicine for disease prevention and illness healing; empower PHC with digital technology; ensure access to medicinal products and appropriate technologies; and last, strengthen global partnership and international health cooperation. The Initiative will enrich the content of quality development of PHC, build consensus, and put forward policies for quality development of PHC in China in the new era, which are expected to make contributions in accelerating global actions.

Development and psychometric testing of a Chinese version of the postnatal care experience scale for postpartum women.

BACKGROUND: Postnatal period is a critical transitional phase in the lives of mothers and newborn babies. In recent years the importance on promoting a positive experience of care following childbirth is increasingly emphasized. Yet published evidence of the methodological and psychometric quality of instruments to evaluate women's experience of comprehensive postnatal care is still lacking. OBJECTIVE: This study aimed to develop and validate a unique scale (the Chinese version of the Postnatal Care Experience Scale, PCES) to measure women's overall experience of care during postnatal periods. METHODS: The PCES instrument was developed and validated over three phases, including item development, scale development, and scale evaluation. The item pool of the PCES was generated through existing literature and in-depth semi-structured interviews, followed by assessment of content validity and rating of importance and feasibility of items through two-round Delphi surveys. Psychometric properties were examined in a convenience sample of 736 postpartum women. Both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to assess the construct validity of the developed PCES. The relationship between the total PCES score and the global item construct was estimated using Pearson product-moment coefficient. Reliability was assessed using Cronbach's alpha and Spearman Brown coefficients. RESULTS: The content validity index of the Chinese version PCES was 0.867. Following item reduction analysis, this instrument consisted of 30 five-point Likert items. The Kaiser-Meyer-Olkin statistic was 0.964 and the chi-square value of the Bartlett spherical test was 11665.399 (P < .001). The scale explained 75.797% of the total variance and consisted of three subscales, including self-management, social support, and facility- and community-based care. The Pearson correlation coefficient between the total PCES score and the global item construct was 0.909. The CFA showed that the 3-factor model had suitable fitness for the data. Cronbach's alpha value and Spearman-Brown Split-half reliability for the total scale were 0.979 and 0.941, respectively. CONCLUSIONS: The newly developed 30-item PCES is a psychometrically reliable and valid instrument that assesses women's overall experience of postnatal care. Future research should aim to use the PCES in various populations to obtain further evidence for its validity and reliability.

Inhibiting G6PD by quercetin promotes degradation of EGFR T790M mutation.

EGFRT790M mutation causes resistance to the first-generation tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, the therapeutic options for sensitizing first TKIs and delaying the emergence of EGFRT790M mutant are limited. In this study, we show that quercetin directly binds with glucose-6-phosphate dehydrogenase (G6PD) and inhibits its enzymatic activity through competitively abrogating NADP+ binding in the catalytic domain. This inhibition subsequently reduces intracellular NADPH levels, resulting in insufficient substrate for methionine reductase A (MsrA) to reduce M790 oxidization of EGFRT790M and inducing the degradation of EGFRT790M. Quercetin synergistically enhances the therapeutic effect of gefitinib on EGFRT790M-harboring NSCLCs and delays the acquisition of the EGFRT790M mutation. Notably, high levels of G6PD expression are correlated with poor prognosis and the emerging time of EGFRT790M mutation in patients with NSCLC. These findings highlight the potential implication of quercetin in overcoming EGFRT790M-driven TKI resistance by directly targeting G6PD.

AFTR: A Robustness Multi-Sensor Fusion Model for 3D Object Detection Based on Adaptive Fusion Transformer.

Multi-modal sensors are the key to ensuring the robust and accurate operation of autonomous driving systems, where LiDAR and cameras are important on-board sensors. However, current fusion methods face challenges due to inconsistent multi-sensor data representations and the misalignment of dynamic scenes. Specifically, current fusion methods either explicitly correlate multi-sensor data features by calibrating parameters, ignoring the feature blurring problems caused by misalignment, or find correlated features between multi-sensor data through global attention, causing rapidly escalating computational costs. On this basis, we propose a transformer-based end-to-end multi-sensor fusion framework named the adaptive fusion transformer (AFTR). The proposed AFTR consists of the adaptive spatial cross-attention (ASCA) mechanism and the spatial temporal self-attention (STSA) mechanism. Specifically, ASCA adaptively associates and interacts with multi-sensor data features in 3D space through learnable local attention, alleviating the problem of the misalignment of geometric information and reducing computational costs, and STSA interacts with cross-temporal information using learnable offsets in deformable attention, mitigating displacements due to dynamic scenes. We show through numerous experiments that the AFTR obtains SOTA performance in the nuScenes 3D object detection task (74.9% NDS and 73.2% mAP) and demonstrates strong robustness to misalignment (only a 0.2% NDS drop with slight noise). At the same time, we demonstrate the effectiveness of the AFTR components through ablation studies. In summary, the proposed AFTR is an accurate, efficient, and robust multi-sensor data fusion framework.