[Research Progress of Targeted Therapy for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma --Review].

Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a relatively inert B lymphocyte proliferative disease. In recent years with the launch of new drugs, chemotherapy has been gradually replaced by targeted therapy, which significantly prolongs the survival of patients and reduces the side effects of treatment. At present, BTK inhibitors, PI3K inhibitors, spleen tyrosine kinase (SYK) inhibitors and BCL-2 inhibitors are the most studied targeted therapeutic drugs for CLL/SLL. This article reviews the research progress of different types of targeted therapeutic drugs in the treatment of CLL/SLL.

Tandem autologous hematopoietic stem cell transplantation for patients with multiple myeloma: a systematic review and meta-analysis.

To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched, and 10 eligible studies were included after data extraction and quality evaluation. Meta-analysis showed that compared to single autologous hematopoietic stem cell transplantation, tandem auto-HSCT does not improve OS, EFS or efficacy in MM patients, and may even lead to higher treatment-related mortality (TRM). MM patients who received autologous tandem allogeneic HSCT did not achieve better response compared to tandem autologous HSCT. In summary, compared to single autologous hematopoietic stem cell transplantation, tandem autologous hematopoietic stem cell transplantation cannot provide survival advantages for MM patients, and MM patients cannot benefit from autologous tandem allogeneic hematopoietic stem cell transplantation.

In Situ Formed Robust Solid Electrolyte Interphase with Organic-Inorganic Hybrid Layer for Stable Zn Metal Anode.

Stabilizing the Zn anode/electrolyte interface is critical for advancing aqueous zinc ion storage technologies. Addressing this challenge helps minimize parasitic reactions and controls the formation of Zn dendrites, which is fundamental to achieving highly reversible Zn electrochemistry. In this study, 2% by volume of dimethyl sulfoxide (DMSO) is introduced into the baseline zinc sulfate (ZS) electrolyte, which acts as an efficient regulator to form a robust solid-electrolyte interphase (SEI) on the Zn anode. This innovative approach enables uniform Zn deposition and does not substantially modify the Zn2+ solvation structure. The Zn||Zn symmetric cell exhibits an extended cycle life of nearly one calendar year (>8500 h) at a current density of 0.5 mA cm-2 and an areal capacity of 0.5 mAh cm-2. Impressive full cell performance can be achieved. Specifically, the Zn||VS2 full cell achieves an areal capacity of 1.7 mAh cm-2, with a superior negative-to-positive capacity ratio of 2.5, and an electrolyte-to-capacity ratio of 101.4 µL mAh-1, displaying remarkable stability over 1000 cycles under a high mass loading of 11.0 mg cm-2 without significant degradation. This innovative approach in electrolyte engineering provides a new perspective on in situ SEI design and furthers the understanding of Zn anode stabilization.

Mouse serum albumin induces neuronal apoptosis and tauopathies.

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

Quality appraisal of clinical practice guidelines addressing massage interventions using the AGREE II instrument.

OBJECTIVE: The purpose of this study was to systematically evaluate the methodological quality of massage-related clinical practice guidelines (CPGs)/consensus on massage using the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument and to summarize the current status of recommendations in the CPGs. METHODS: The Chinese National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database (VIP), China Biology Medicine disc (CBM), PubMed, Embase, and guideline websites (such as the Chinese Medical Ace Base, the China Association of Chinese Medicine, the World Health Organization, Guideline International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network) were searched from inception to October 31, 2022. In addition, the reference lists of relevant studies were reviewed to identify domestic and overseas massage CPGs/consensus. The search terms adopted a combination of subject words and free words, mainly including traditional Chinese medicine, complementary therapies, Tuina, massage, manipulation, chiropractic/osteopathic, spinal, acupressure, guideline, and consensus. Two researchers independently completed the eligible records and extracted the data. Before the formal research, calibrations were performed twice on AGREE II, and all reviewers completed the pilot test three times until they understood and reached an agreement on the assessment items. Three researchers appraised the methodological quality of the included guidelines using the AGREE II instrument and calculated the overall intraclass correlation coefficient (ICC) of agreement. RESULTS: The evaluation results showed that among the 49 eligible CPGs/consensus, 4 (8.2%) CPGs/consensus were considered "recommended", 15 (30.6%) CPGs/consensus were considered "recommended with modifications", and 30 (61.2%) CPGs/consensus were considered "not recommended", while the consensus was considered "not recommended". Generally, the scores in the six domains of the guidelines were all higher than the consensus. Evaluation results for the overall quality of 36 CPGs showed that 4 (11%) were "good quality", 15 (42%) were "sufficient quality" and 17 (47%) were "lower quality". The AGREE II quality scores of domains ranged from 0.30 to 0.75 ([ICC = 0.993, 95% CI (0.992, 0.995)]). The domain of scope and purpose (domain 1), with a median score of 0.75 (0.52~0.91), performed best in the guidelines with AGREE II, and stakeholder involvement (domain 2) [median 0.39 (0.31~0.56)] and application (domain 5) [median 0.30 (0.17~0.47] obtained lower scores. The consensus score of domain 1 was better at 26.0 (21.6~44.8), followed by rigor of development (domain 3) with a score of 18.0 (10.0~28.9). A total of 119 massage-related recommendations were extracted from 49 guidelines/consensuses, including "in favor" (102, 85.7%), "against" (9, 7.6%), and "did not make recommendations" (8, 6.7%). CONCLUSION: The overall quality of the included guidelines was low, and most of the guidelines were not "recommended". In future guideline updates, the existing evidence should be used, the professional composition of members of the expert group should be enriched, and patients' values and preferences should be fully considered. It is necessary to clearly propose recognizable recommendations and strengthen the rigor and standardization of guideline formulation. Thus, clear standard guidelines can be formulated to better guide clinical practice.

Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer's disease diagnosis and differential diagnosis.

Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer's disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.

The effects of exercise on insomnia disorders: An umbrella review and network meta-analysis.

OBJECTIVE: To summarize the evidence of various exercise modalities on population with insomnia disorders. METHOD: PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible studies published from inception to October 2022 and updated on September 2023. Systematic reviews with meta-analyses and randomized controlled trials designed to investigate the effect of various exercise modalities on population with insomnia were eligible. RESULTS: A total of 4 SRs with (very) low methodological quality and 1034 participants in 10 network meta-analyses explored the association between different types and intensity exercise modalities with insomnia disorders. Various exercise modalities could significantly improve total sleep time and sleep quality and alleviate insomnia severity. Compared to passive control, moderate aerobic exercise, moderate aerobic exercise combined with light intensity strength and mind-body exercise can improve sleep efficiency and reduce wake after sleep onset by objectively measured. Moderate intensity strength, light intensity strength and mind-body exercise can improve sleep efficiency subjectively measured; mind-body exercise can reduce sleep onset latency and wake time after sleep onset, and increase total sleep time; moderate aerobic exercise can reduce sleep onset latency. Moderate intensity strength, light intensity strength, mind body exercise and moderate aerobic exercise combined with light intensity strength can the severity of insomnia and improv sleep quality. CONCLUSION: Exercise had a positive effect on relief insomnia and improve sleep quality. Moderate aerobic exercise, mind-body exercise and moderate aerobic exercise combined with light intensity strength play an important role in improving the sleep quality in people with insomnia disorders.

Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115.

STING (also known as MITA) is an adaptor protein that mediates cytoplasmic DNA-triggered signaling, and aberrant activation of STING/MITA by cytosolic self-DNA or gain-of-function mutations causes severe inflammation. Here, we show that STING-mediated inflammation and autoimmunity are promoted by RNF115 and alleviated by the RNF115 inhibitor disulfiram (DSF). Knockout of RNF115 or treatment with DSF significantly inhibit systemic inflammation and autoimmune lethality and restore immune cell development in Trex1-/- mice and STINGN153S/WT bone marrow chimeric mice. In addition, knockdown or pharmacological inhibition of RNF115 substantially downregulate the expression of IFN-α, IFN-γ and proinflammatory cytokines in PBMCs from patients with systemic lupus erythematosus (SLE) who exhibit high concentrations of dsDNA in peripheral blood. Mechanistically, knockout or inhibition of RNF115 impair the oligomerization and Golgi localization of STING in various types of cells transfected with cGAMP and in organs and cells from Trex1-/- mice. Interestingly, knockout of RNF115 inhibits the activation and Golgi localization of STINGN153S as well as the expression of proinflammatory cytokines in myeloid cells but not in endothelial cells or fibroblasts. Taken together, these findings highlight the RNF115-mediated cell type-specific regulation of STING and STINGN153S and provide potential targeted intervention strategies for STING-related autoimmune diseases.

OTUB1 Targets CHK1 for Deubiquitination and Stabilization to Facilitate Lung Cancer Progression and Radioresistance.

PURPOSE: Radioresistance of lung cancer poses a significant challenge when it comes to the treatment of advanced, recurrent, and metastatic cases. Ovarian tumor domain ubiquitin aldehyde binding 1 (OTUB1) is a key member of the deubiquitinase OTU superfamily. This protein is involved in various cellular functions, including cell proliferation, iron death, lipid metabolism, and cytokine secretion as well as immune response processes. However, its specific role and molecular mechanism in lung cancer radioresistance remain to be clarified. METHODS AND MATERIALS: The expression levels of OTUB1 in paired lung cancer tissues were determined by immunohistochemistry. In vitro and in vivo experiments were conducted to investigate the impact of OTUB1 on the growth and proliferation of lung cancer. Coimmunoprecipitation and Western blotting techniques were performed to examine the interaction between OTUB1 and CHK1. The DNA damage response was measured by comet tailing and immunofluorescence staining. KEGG pathways and Gene Ontology terms were analyzed based on RNA sequencing. RESULTS: Our findings reveal a high frequency of OTUB1 overexpression, which is associated with an unfavorable prognosis in patients with lung cancer. Through comprehensive investigations, we demonstrate that OTUB1 depletion impairs the process of DNA damage repair and overcomes radioresistance. In terms of the underlying mechanism, our study uncovers that OTUB1 deubiquitinates and stabilizes CHK1, which enhances CHK1 stability, thereby regulating DNA damage and repair. Additionally, we identify CHK1 as the primary downstream effector responsible for mediating the functional effects exerted by OTUB1 specifically in lung cancer. Importantly, OTUB1 has the potential to be a valuable marker for improving the efficacy of radiation therapy for lung adenocarcinoma. CONCLUSIONS: These findings unveil a novel role for OTUB1 in enhancing radioresistance by deubiquitination and stabilization of the expression of CHK1 in lung cancer and indicate that targeting OTUB1 holds great potential as an effective therapeutic approach for enhancing the efficacy of radiation therapy in lung cancer.

Efficacy of Endovascular Repair Using Single Left Common Carotid Artery Stent Combined with Castor Single-Branched Stent-Graft in the Treatment of Regional Diseases of Zone 2 of the Aorta.

PURPOSE: To observe the short-term efficacy of thoracic endovascular aortic repair (TEVAR) using a single left common carotid artery chimney stent combined with a Castor single-branched stent-graft (SC-TEVAR) in the treatment of zone 2 (Z2) aortic diseases. MATERIALS AND METHODS: To conduct a retrospective analysis of 20 patients with Z2 aortic diseases who were treated in our department from June 2021 to April 2022. The lesions included true aortic degenerative aneurysms with diameter ≥5.0 cm and penetrating aortic ulcers with depth >1.0 cm or basal width >2.0 cm. All 20 patients accepted the SC-TEVAR treatment, which was a new hybrid method to assure the flow of the left common carotid artery (LCCA) and left subclavian artery (LSA). This method was defined as a concomitant chimney stent for LCCA and a Castor single-branched stent graft for the aorta and LSA. The baseline data and intraoperative data were collected to evaluate the safety and efficacy of this method. The patency of the target blood vessel and any associated complications were evaluated at 1 and 6 months postoperatively, to analyze the safety and efficacy of this new method. RESULTS: After discharge from the hospital, all patients were followed up by a specific follow-up team. At 6 monthly follow-up period, there were no cardiac events, stroke, hemiplegia, type I endoleak, type II endoleak, proximal stent graft-induced new entries, distal stent graft-induced new entries, wound infection, or bleeding. Only 1 patient developed an inguinal wound hematoma and got conservative treatment. Importantly, no patients developed stenosis or occlusion of the LCCA or LSA. The patency of branched arteries was 100%. The technical success rate was 90%. CONCLUSION: SC-TEVAR appears to be a new and relatively simple, safe, and effective treatment for Z2 aortic diseases. CLINICAL IMPACT: This was a single-center retrospective cohort study. A total of 20 patients with zone 2 aortic diseases accepted a new hybrid surgical method named SC-TEVAR. This method was not complicated and could be finished with only 3 peripheral artery exposure. The result showed no mortality, 100% patency of the branch artery, and 90% of technical success in 6 months of follow-up time. SC-TEVAR showed a satisfactory result in this retrospective study and could be promoted as an easy method to treat zone 2 aortic diseases.

Giant lipoma in the Retzius space resected under laparoscopy: A case report.

Lipoma is a common type of benign soft tissue tumor that can occur in the shoulders, neck and back, in addition to other body parts. The Retzius space is a small anatomical space between the pubic symphysis and the bladder located extraperitoneally and filled with loose fatty connective tissue. Giant lipomas are rare in the Retzius space. A 61-year-old Chinese male arrived at Beijing Yanhua Hospital (Beijing, China) due to frequent urination, and CT scan images of the lower abdomen observed a large pelvic mass and left inguinal hernia. Preoperative clinical manifestations and auxiliary examination suggested that the tumor originated from the urinary bladder wall. The maximum tumor diameter was ~25 cm and abdominal pressure was increased. Therefore, laparoscopic pelvic tumor resection combined with inguinal hernia repair was attempted. Intraoperatively, the tumor was found to originate from the Retzius space and the postoperative pathological diagnosis was lipoma. The present case report may serve as a reference for minimally invasive treatment of this type of rare disease in future.

GV-971 attenuates α-Synuclein aggregation and related pathology.

RATIONALE: Synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), share a distinct pathological feature, that is, a widespread accumulation of α-synuclein (α-syn) in the brain. There is a significant clinical unmet need for disease-modifying treatments for synucleinopathies. Recently, a seaweed-derived mixture of oligosaccharides sodium oligomannate, GV-971, was approved for Phase 2 clinical trials for PD. This study aimed to further evaluate the therapeutic effects of GV-971 on synucleinopathies using cellular and animal models and explore its associated molecular mechanisms. METHODS: α-Syn aggregation was assessed, in vitro and ex vivo, by ThT assay. A dopaminergic neuron cell line, Prnp-SNCAA53T mice, and brain slices from PD and DLB patients were used to determine the efficacy of GV-971 in ameliorating α-syn pathology. Measurements of motor functions, including pole, cylinder, and rotarod tests, were conducted on Prnp-SNCAA53T mice 4 weeks after intragastric administration of GV-971 (200 mg day-1 kg-1 ). RESULTS: GV-971 effectively prevented α-syn aggregation and even disassembled pre-aggregated α-syn fibrils, in vitro and ex vivo. In addition, GV-971 was able to rescue α-syn-induced neuronal damage and reduced release of extracellular vesicles (EVs), likely via modulating Alix expression. In the Prnp-SNCAA53T mouse model, when treated at the age of 5 months, GV-971 significantly decreased α-syn deposition in the cortex, midbrain, and cerebellum regions, along with ameliorating the motor dysfunctions. CONCLUSIONS: Our results indicate that GV-971, when administered at a relatively early stage of the disease process, significantly reduced α-syn accumulation and aggregation in Prnp-SNCAA53T mice. Furthermore, GV-971 corrected α-syn-induced inhibition of EVs release in neurons, contributing to neuronal protection. Future studies are needed to further assess GV-971 as a promising disease-modifying therapy for PD and other synucleinopathies.

Electrolyte Modulation Strategies for Low-Temperature Zn Batteries.

Aqueous rechargeable Zn metal batteries (ARZBs) are extensively studied recently because of their low-cost, high-safety, long lifespan, and other unique merits. However, the terrible ion conductivity and insufficient interfacial redox dynamics at low temperatures restrict their extended applications under harsh environments such as polar inspections, deep sea exploration, and daily use in cold regions. Electrolyte modulation is considered to be an effective way to achieve low-temperature operation for ARZBs. In this review, first, the fundamentals of the liquid-solid transition of water at low temperatures are revealed, and an in-depth understanding of the critical factors for inferior performance at low temperatures is given. Furthermore, the electrolyte modulation strategies are categorized into anion/concentration regulation, organic co-solvent/additive introduction, anti-freezing hydrogels construction, and eutectic mixture design strategies, and emphasize the recent progress of these strategies in low-temperature Zn batteries. Finally, promising design principles for better electrolytes are recommended and future research directions about high-performance ARZBs at low temperatures are provided.

Targeting CENP-E augments immunotherapy in non-small cell lung cancer via stabilizing PD-L1.

Centromere-associated protein E (CENP-E) plays a critical role in mitosis and chromosome misalignment, which may represent a potential therapeutic target in tumors. CENP-E is frequently overexpressed in lung cancer and act as a driver gene. However, it remains unclear whether CENP-E regulates the immune microenvironment in non-small cell lung cancer (NSCLC). Our study revealed that CENP-E is highly expressed and predicts a worse survival in NSCLC patients; inhibition of CENP-E leads to an upregulation of PD-L1 expression, consequently impacting the immune microenvironment of NSCLC by modulating the balance between CD8+ T cells and regulatory T cells (Tregs). Mechanistically, we demonstrated that downregulation of CENP-E could stabilize PD-L1 mRNA through the targeting of its 3'UTR by TTP. The genetic knockdown or pharmacological inhibition of CENP-E, in combination with PD-L1 antibody, could enhance the antitumor effect in NSCLC. Thus, our findings have revealed a role of CENP-E in immunotherapy and suggest that combination of CENP-E inhibitor with PD-L1 antibody could be an effective treatment option for NSCLC.

The Role of Thoracic Vertebral Body Dosimetry in Minimizing Acute Hematologic Toxicities of Patients With Non-Small Cell Lung Cancer Receiving Lung Radiation Therapy and Immunotherapy.

PURPOSE: Hematologic toxicities (HTs) are among the most common toxicities of combined immunotherapy and radiation therapy (RT). It remains essential to prevent RT-induced HTs because they can cause treatment discontinuation (influencing antitumoral effects) and because lymphopenia might dampen the effects of immunotherapy. To date, there are no studies examining the effect of thoracic vertebral body (TVB) RT dose on HTs in patients with non-small cell lung cancer receiving combined lung RT and programmed cell death (ligand) 1 immunotherapy. METHODS AND MATERIALS: For standardization, all doses were reported as 2-Gy equivalents (EQD2). Mirroring publications before the immunotherapy era, TVB volumes referred to T1-T10, and specific dosimetric parameters (DmeanEQD2, V5EQD2-V60EQD2) were analyzed. Logistic regression estimated associations between grade ≥3 HTs (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability (NTCP) models were constructed by logistic regression analysis modeling for HT3+. Receiver operating characteristic (ROC) analysis delineated TVB dosimetric thresholds, the stratification of which was able to evaluate post-RT absolute lymphocyte count and immunotherapy responses. Areas under the curve (AUCs) for NTCP models were corroborated by bootstrapping (optimism-corrected) methodology. RESULTS: In 132 patients, there were 26 (19.7%) instances of HT3+. On multivariate analysis, DmeanEQD2 and V5EQD2 to V20EQD2 were associated with HT3+ (P < .05 for all). The NTCP models illustrated a 50% probability of HT3+ at a DmeanEQD2 = 39.8 Gy, V5EQD2 = 87.4%, V10EQD2 = 77.0%, and V20EQD2 = 68.4%. ROC analysis delineated optimal thresholds of HT3+ with DmeanEQD2 ± 30.2 Gy, V5EQD2 ± 69.1%, V10EQD2 ± 64.6%, and V20EQD2 ± 53.5%. Patients treated with values above those cutoffs had over double the risk of HT3+, with significant differences in post-RT absolute lymphocyte count and immunotherapy responses (P < .05 for all). AUCs for each individual parameter ranged from 0.743 to 0.798, and combining all 4 aforementioned cutoffs into a ROC curve resulted in a qualitatively higher AUC (0.836). CONCLUSIONS: This hypothesis-generating work suggests that TVB dosimetry may equate with HT3+ in patients with non-small cell lung cancer undergoing combined lung RT/immunotherapy. Applying TVB dose constraints in this population could reduce HT3+ and avoid dampening of immunotherapy responses, but prospective validation is required.

Comparative efficacy of exercise modalities on sleep quality in populations with sleep disorders: A systematic review and network meta-analysis.

The effect of various exercise modalities on people with sleep disorders remains unclear. This network meta-analysis aims to explore the effects of various exercise modalities in improving sleep quality in people with sleep disorders. Four electronic databases were searched from inception to April 8, 2023. We conducted pairwise meta-analyses and frequentist network meta-analyses with random effects models. A total of 17 randomized controlled trials enrolled 1090 participants were included. Compared with passive control, with moderate-to-low certainty of evidence, mind-body exercise combined with treatment as usual [standard mean difference (SMD) = -2.26, 95% confidence interval (CI) (-3.29, -1,24)], moderate aerobic exercise combined with light strength exercise [SMD = -1.26, 95% CI (-2.22, -0.31)], mind-body exercise [SMD = -0.81, 95% CI (-1.37, -0.25)] and moderate aerobic exercise [SMD = -0.75, 95% CI (-1.38, -0.13)] were more effect in improving sleep disorders. Various exercise modalities have favorable effects on sleep quality for people with sleep disorders compared with passive control. However, due to the low quality of evidence, well-designed trials should be conducted to elucidate these promising findings in the future.

Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear / 神经科学通报·英文版

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.

Enhancing long-term frequency stability of a single-mode optoelectronic oscillator based on phase conjugation.

We propose and experimentally demonstrate what we believe to be a novel single-mode optoelectronic oscillator (OEO) with low frequency drift based on phase conjugation. The long-term frequency stabilization of the OEO is achieved by using photonic microwave phase-conjugate passive compensation. Besides, since there happens to be a nonlinear coupled double loop structure in the OEO, single-mode oscillation can be achieved. The experimental results show that the side mode suppression ratio (SMSR) of the radio frequency (RF) signal from the OEO at 9.93 GHz is enhanced from 5 dB to 68 dB after side mode suppression, and the maximum frequency drift within 600 s reduced from 1.51 ppm to 0.04 ppm, optimized by a factor of about 40. The OEO has a simple structure, no external injection, and the phase noise is not limited by the injected signal.

The Relationship Between Bone Metabolism and Peripheral Artery Disease in Patients on Hemodialysis: The Potential Role of Osteocalcin.

Introduction: To examine the factors associated with PAD, with a specific focus on bone metabolism factors such as osteocalcin. Methods: This cross-sectional study examined factors about demographic, clinical, and laboratory parameters including bone metabolism biomarkers in hemodialysis patients. The ankle-brachial index (ABI) was measured in all patients, with PAD diagnosed as an ABI <0.9. Results: Out of the 71 patients, PAD was found in 23 individuals. These patients had an average age of 63.5±13.0 years, with 59.2% being male. Compared to non-PAD patients, those with PAD were older, had a lower proportion of males, and had a higher prevalence of diabetes and coronary artery disease. Among the factors related to bone metabolism, only osteocalcin exhibited a significant increase in the PAD group compared to the non-PAD group. Conclusion: PAD in patients on hemodialysis was independently linked to high levels of osteocalcin in the bloodstream, indicating the presence of bone metabolism disorders.

STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition.

Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double-stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2-deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1-BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2-mutant tumors is elucidated.