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Background: The increasing prevalence of cognitive impairment poses substantial risks to older adults, particularly those with chronic diseases. While existing studies have examined the connection between the empty nest phenomenon and cognitive function, few have attempted to consider endogeneity issues within this relationship, with limited attention given to older adults with chronic diseases. This study investigates the impact of empty nest status on cognitive function among rural Chinese older adults with chronic diseases and explores the possible mechanisms underlying this effect. Methods: A cross-sectional study involved 365 older adults aged 60 or above with chronic diseases in rural areas of Shaanxi province, northwest China. Cognitive function was measured using the Mini-Mental State Examination. Multiple regression models and the instrumental variable (IV) method were employed to examine the association between empty nest and cognitive function. Results: Among the 365 older adults aged 60 or above with chronic diseases, 43% experienced cognitive impairment. Results from both multiple regression and IV analyses consistently demonstrate a significant association between empty nest status and higher cognitive function scores (β = 1.757, p = 0.007; β = 3.682, p = 0.034, respectively). Mechanism analysis further supports that the positive association may arise from empty nesters receiving more social support from children and friends, and perceiving loneliness experiences as inadequate. Heterogeneity analysis reveals that the association between empty nest status and cognitive function is more pronounced among male adults with chronic diseases. Conclusions: This study challenges the notion that empty nest status is a risk factor for cognitive decline in older adults with chronic diseases in rural China. The positive impact is attributed to the robust social relationships of empty nesters, encompassing sustained support from their social network, and the absence of an increase in loneliness. Therefore, future interventions aimed at improving cognitive function in older adults may benefit from promoting the development of social relationships. [ABSTRACT FROM AUTHOR]

Li‐rich cathode materials (LRMs) are regarded as the key cathode candidates for next‐generation lithium‐ion batteries(LIBs) because of their high specific capacity and environmental friendliness. However, LRMs encounter poor cyclability and low initial coulombic efficiency (ICE) hindering their practical application. Herein, a general near‐surface in situ reconstruction strategy is proposed of constructing the Li/O dual vacancies and spinel‐carbon dual coating layers on the surface of LRMs concurrently to improve Li+ storage performance. The as‐prepared LRMs exhibit a greatly strengthened specific capacity of 283 mAh g−1 with an enhanced ICE of 94% and long‐term cyclability of 91% retention after 200 cycles compared with the pristine LRMs (212 mAh g−1 with an ICE of 65%, 76% retention after 200 cycles). Furthermore, it is theoretically revealed that O vacancies (Ov) prefer to occur at the interface of the C2/m and R3¯$\bar{3}$m phases to mitigate lattice stress, rather the O sites in individual C2/m or R3¯$\bar{3}$m phase with more coordinated atoms. Besides, Li ions exhibit lower migration energy from C2/m phase to R3¯$\bar{3}$m phase with the Ov located at the lattice interface. Therefore, this strategy opens a new avenue in the design perspective of the LRMs' near‐surface for high‐energy‐density LIBs. [ABSTRACT FROM AUTHOR]

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B‐cell lymphoma‐3 (Bcl‐3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl‐3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl‐3 in macrophages can regulate glycolysis‐related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl‐3 was able to promote the interferon gamma/lipopolysaccharide‐induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl‐3 may be a candidate gene for regulating M1 polarization in macrophages. [ABSTRACT FROM AUTHOR]

Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions. Microglia undergo rapid phenotype changes in response to tissue disturbances but the impact of these changes on neuronal networks is unclear. Here, the authors show that microglia contribute to neuronal synchrony in acute brain slices, while their marked phenotypic transformation is influenced by injury-related focal ATP events. [ABSTRACT FROM AUTHOR]

Objectives: In middle-income countries, poor physician-patient communication remains a recognized barrier to enhancing healthcare quality and patient satisfaction. This study investigates the influence of provider-patient communication skills on healthcare quality and patient satisfaction in the rural primary healthcare setting in China. Methods: Data were collected from 504 interactions across 348 rural primary healthcare facilities spanning 21 counties in three provinces. Using the Standardized Patient method, this study measured physician-patient communication behaviors, healthcare quality, and patient satisfaction. Communication skills were assessed using the SEGUE questionnaire framework. Multivariate linear regression models and multivariate logistic regression models, accounting for fixed effects, were employed to evaluate the impact of physicians' communication skills on healthcare quality and patient satisfaction. Results: The findings indicated generally low provider-patient communication skills, with an average total score of 12.2 ± 2.8 (out of 24). Multivariate regression models, which accounted for physicians' knowledge and other factors, demonstrated positive associations between physicians' communication skills and healthcare quality, as well as patient satisfaction (P < 0.05). Heterogeneity analysis revealed stronger correlations among primary physicians with lower levels of clinical knowledge or more frequent training. Conclusion: This study emphasizes the importance of prioritizing provider-patient communication skills to enhance healthcare quality and patient satisfaction in rural Chinese primary care settings. It recommends that the Chinese government prioritize the enhancement of provider-patient communication skills to improve healthcare quality and patient satisfaction. [ABSTRACT FROM AUTHOR]

To investigate the influence mechanism of the light-off characteristics and secondary pollutants (N2O and NH3) of the Pd/Rh catalytic converter for natural gas engines, a global model of the catalytic converter and a more comprehensive catalytic reaction mechanism were first established. Further, the model and the catalytic reaction mechanism were validated by using experimental data. Then, the effects of exhaust temperature and exhaust composition (H2O, O2, and H2 concentrations) on the catalytic converters were investigated. The results showed that a higher temperature reduced the light-off time t50 of NO and CO. The production of N2O decreased to 0 at high temperatures due to the reduction reactions of R14 (N2O+H2 = H2O+N2) and R16 (N2O+CO = CO2 + N2). NH3 would form at the temperature above 825 K, and the required H2 originated from SR and WGS reactions. Increasing the H2 concentration promoted the conversion of NO and CO. When the temperature exceeds 600 K, increasing the H2 concentration decreases the production of N2O. H2O has the opposite effect on the production of N2O and NH3 at high temperatures. Increasing the content of H2O increased the conversion of NO and inhibited the conversion of CO. O2 concentration at 4000 × 10−6 is beneficial to reduce secondary pollutants of N2O and NH3. At the condition of 730–820 K and 4000 × 10−6 O2, the productions of N2O and NH3 were reduced to 0. This study contributes to the efficient application of Pd/Rh catalytic converters and further enhances the emission reduction of natural gas engines. [ABSTRACT FROM AUTHOR]

Non-hydraulic root signals (nHRS) are affirmed as a unique positive response to soil drying, and play a crucial role in regulating water use efficiency and yield formation in dryland wheat production. Strigolactones (SLs) can enhance plant drought adaptability. However, the question of whether strigolactones enhance grain yield and water use efficiency by regulating nHRS and antioxidant defense systems in dryland wheat remains unanswered. In this study, pot experiments were conducted to investigate the effects of strigolactones on nHRS, antioxidant defense system, and grain yield and water use efficiency in dryland wheat. The results showed that external application of SLs increased drought-induced abscisic acid (ABA) accumulation and activated an earlier trigger of nHRS at 73.4% field capacity (FC), compared to 68.5% FC in the control group (CK). This phenomenon was mechanically associated with the physiological mediation of SLs. The application of SLs significantly enhanced the activities of leaf antioxidant enzymes, reduced ROS production, and mitigated oxidative damage to lipid membrane. Additionally, root biomass, root length density, and root to shoot ratio were increased under strigolactone treatment. Furthermore, exogenous application of SLs significantly increased grain yield by 34.9% under moderate drought stress. Water use efficiency was also increased by 21.5% and 33.3% under moderate and severe drought conditions respectively, compared to the control group (CK). The results suggested that the application of strigolactones triggered earlier drought-sensing mechanism and improved the antioxidant defense ability, thus enhancing grain yield and water use efficiency in dryland wheat production. [ABSTRACT FROM AUTHOR]

The discrete element method was used to simulate the friction process of copper-based graphite composite materials in order to analyze the influence of pore structure on the solid lubricants migration in metal-based self-lubricating materials. And the near-surface pore volume evolution was considered in the simulation. The simulation results showed that the graphite particle motion depth and the migration channel increased gradually and tended to stable during friction. The near-surface pore structure has an important influence on the graphite migration and the tribological properties of the composite: the larger the migration channel was, the greater the graphite migration speed was; with the increase in migration channel, the graphite average critical migration depth decreased first then increased, the number of the film-forming particles first increased and then decreased; the greater the migration channel volume was, the more worn particles number were. The numerical simulation was confirmed by experimental analysis on a self-made in-situ observation tribometer, the experimental results were consistent with the numerical simulation results. [ABSTRACT FROM AUTHOR]

Reducing the cost and improving the electrocatalytic activity are the key to developing high efficiency electrocatalysts for oxygen evolution reaction (OER). Here, bimetallic NiFe-based metal-organic framework (MOF) was prepared by solvothermal method, and then used as precursor to prepare NiFe-based MOF-derived materials by pyrolysis. The effects of different metal ratios and pyrolysis temperatures on the sample structure and OER electrocatalytic performance were investigated and compared. The experimental results showed that when the metal molar ratio was Fe: Ni = 1:5 and the pyrolysis temperature was 450°C, the sample (FeNi5-MOF-450) exhibits a composite structure of NiFe2O4/FeNi3/C and owns the superior electrocatalytic activity in OER. When the current density is 100 mA·cm−2, the overpotential of the sample was 377 mV with Tafel slope of 56.2 mV·dec−1, which indicates that FeNi5-MOF-450 exhibits superior electrocatalytic performance than the commercial RuO2. Moreover, the long-term stability of FeNi5-MOF-450 further promotes its development in OER. This work demonstrated that the regulatory methods such as component optimization can effectively improve the OER catalytic performance of NiFe-based MOF-derived materials. [ABSTRACT FROM AUTHOR]

Both the adsorption/dissociation of water molecules and hydrogen intermediate (H*) are the major limitations to hydrogen evolution reaction (HER). Herein, the modulation of electronic structure and geometric configuration are combined to design one-dimensional electrocatalyst with outstanding HER activity in a wide pH range. The catalyst was composed of molybdenum trioxide doped molybdenum nickel alloy supported by copper nanowires (MoO3-MoNi4@Cu NWs). As revealed by the experimental characterizations and theoretical calculations, Cu NWs act as the electron donator to MoNi4, resulting in up shift of the d-band center in MoNi4, thus expediting H2O adsorption and dissociation. Moreover, the introduction of amorphous MoO3 sets up a unique geometric configuration on MoNi4 for the accelerated H* transfer via hydrogen-bond and hydrogen spillover. This work provides a synergetic route for constructing HER freeway and promotes further investigations on more versatile electrocatalysis involving H2O or H*. [ABSTRACT FROM AUTHOR]

High-performance electrocatalysts for oxygen evolution reaction (OER) are crucial for water splitting and metal-air batteries. Two-dimensional (2D) metal-organic framework (MOF) has become a new class of efficient OER electrocatalysts due to the rich coordination unsaturated metal nodes, large specific surface area, and adjustable structures. In addition, because inheriting the original microstructure of MOFs and having stronger chemical and mechanical stability, metal/alloy/oxide, metal sulfide/selenide/phosphide, and other compounds derived from 2D MOFs have also shown their unique OER catalytic ability. Here, we briefly introduced the existing reaction mechanism and evaluation parameters of catalyst performance of OER, introduced the synthesis methods and corresponding characterization techniques of 2D MOFs and their derivatives, and summarized the latest progress of 2D MOFs and their derivatives as OER catalysts. Finally, we put forward some views and suggestions on the existing problems hindering the development of 2D MOFs as OER for advancing the field. [ABSTRACT FROM AUTHOR]

With the rapid advancements in flexible wearable electronics, there is increasing interest in integrated electronic fabric innovations in both academia and industry. However, currently developed plastic board-based batteries remain too rigid and bulky to comfortably accommodate soft wearing surfaces. The integration of fabrics with energy-storage devices offers a sustainable, eco-friendly, and pervasive energy solution for wearable distributed electronics. Fabric-type flexible energy-storage devices are particularly advantageous as they conform well to the curved body surface and the various movements associated with wearing habits such as running. This review presents a comprehensive overview of the advances in flexible fabric-type energy-storage devices for wearable electronics, including their significance, construction methods, structure design, hybrid forms with other energy sources, and the existing challenges and future directions. With worldwide efforts on materials and technologies, we hope that progress in this review will revolutionize our way of life. [ABSTRACT FROM AUTHOR]

Single-atomic Fe-N4 is the well-acknowledged active site in iron-nitrogen-carbon (Fe-N-C) material for oxygen reduction reaction (ORR). The adjusting of the electronic distribution of Fe-N4 is promising for further enhancing the performance of the Fe-N-C catalyst. Herein, a phosphorus (P)-doped Fe-N-C catalyst with penta-coordinated single atom sites (FeNPC) is reported for efficient oxygen reduction. Fe K-edge X-ray absorption spectroscopy (XAS) verifies the coordination environment of single Fe atom, while density functional theory (DFT) calculations reveal that the penta-coordination and neighboring doped P atoms can simultaneously change the electronic distribution of Fe-N4 and its adsorption strength of key intermediates, reducing the reaction-free energy of the potential-limiting step. Electrochemical tests validate the remarkable intrinsic ORR activity of FeNPC in alkaline media (a half-wave potential (E1/2) of 0.904 V vs. reversible hydrogen electrode (RHE) and limited current density (JL) of 6.23 mA·cm−2) and an enhanced ORR performance in neutral (E1/2 = 0.751 V, JL = 5.27 mA·cm−2) and acidic media (E1/2 = 0.735 V, JL = 5.82 mA·cm−2) with excellent stability, highlighting the benefits of optimizing the local environment of single-atomic Fe-N4. [ABSTRACT FROM AUTHOR]

As a narrow bandgap semiconductor, transition metal selenides are promising as excellent electrocatalysts for hydrogen evolution reactions (HERs). Herein, using an ultra-thin MOF as the precursor, a Co-doped core–shell shaped NiSe2 based catalyst is successfully constructed by a two-step calcination method as an efficient HER catalyst. Experiments and theoretical calculations indicate that the introduction of Co adjusts the electronic structure of Ni and Se, promoting charge transfer and reducing the energy barrier of the rate-limiting step to accelerate the hydrogen precipitation reaction. In addition, the core–shell structure contributes to mass transport, and the outer carbon layer improves the stability of the catalyst. The optimal catalyst (Ni0.75Co0.25Se2@NC) exhibited satisfactory electrocatalytic activity as evidenced by a low overpotential of −143 mV at a current density of −10 mA cm−2 and a small Tafel slope of 37.5 mV dec−1. This work provides a valuable strategy for fabricating efficient NiSe2 based electrocatalysts for the HER. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) infection can cause cervical and other cancers, including vulva, vagina, penis, anus, or oropharynx. However, in China's northern Henan Province, data on the prevalence and genotype distribution of HPV among women attending gynecology clinics is limited. This study aimed to investigate the current prevalence and genotype distribution of HPV among women attending gynecology clinics in northern Henan Province. Methods: This study included 15,616 women aged 16–81 years old who visited the Xinxiang central hospital's gynecology department between January 2018 and December 2019. HPV DNA was detected by a conventional PCR method followed by HPV type-specific hybridization, which was designed to detect 17 high-risk HPV (HR-HPV) genotypes and 20 low-risk HPV (LR-HPV) genotypes. HPV prevalence and corresponding 95% confidence intervals (95% CI) were calculated using SPSS 18.0. Results: The overall HPV prevalence was 19.7% among women in northern Henan Province. Single, double, and multiple HPV infections accounted for 13.7%, 4.3%, and 1.8% of the total cases. Most infections were caused by HR-HPV (71.8%), and single genotype HPV infection (13.7%) was the most common pattern. The most common HR-HPV genotype was HPV16 (4.3%), followed by HPV52 (3.5%) and HPV58 (2.0%). The most common LR-HPV genotype was HPV6 (1.4%), followed by HPV61 (1.1%) and HPV81 (1.1%). Conclusions: HPV infection is high among women attending gynecology clinics in northern Henan Province. The highest prevalence was found in women less than 20 years old. In northern Henan Province, the 9-valent HPV vaccine is strongly recommended for regular immunization. [ABSTRACT FROM AUTHOR]

While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers. The typical approach to electronics is to integrate sensors, power units, and controlling components on a printed circuit board (PCB). Here, the authors demonstrate a self-powered and fully integrated combination of sensors and controlling components that is woven, rather than integrated onto a PCB, allowing for wearable health monitoring." [ABSTRACT FROM AUTHOR]

In this paper, the coupling effect of water injection and hydrogen enrichment on combustion, performance and emission characteristics of a GDI engine was experimentally and numerically investigated. The engine speed is maintained at 1300 rpm with an excess air/fuel ratio of 1.0. The hydrogen energy substitution ratio is set to 15%. Water/fuel ratio is set to 0.2 and 0.4. The spark timing is kept fixed at −25 °CA ATDC. Results indicated that there exists competing effect between water injection and hydrogen enrichment. Water injection works as a reactivity suppressor, which slows down the overall flame propagation and deteriorates combustion. Whereas, hydrogen enrichment works as a combustion enhancer, which accelerates the combustion and improves the mixing of air-fuel mixture. The overall combustion speed, which is slowed down by water injection, can be largely recovered by hydrogen enrichment. In addition, a reasonable balance between the competing effects of water injection and hydrogen enrichment can make the combustion similar, meanwhile exhibits different emissions performance. Furthermore, the competing effect vanishes when the liquid water is completely vaporized. To some extent, hydrogen enrichment has a more lasting effect on combustion. • Water injection and hydrogen enrichment can be used to regulate combustion. • Water injection works as a reactivity suppressor, which slows down the overall flame propagation and deteriorates combustion. • Hydrogen enrichment works as a combustion enhancer, which accelerates the combustion and promotes combustion. • Water injection can simultaneously reduce NO, HC and CO emissions however at the expense of engine performance. • A balance between water injection and hydrogen enrichment is beneficial for emission control. [ABSTRACT FROM AUTHOR]

This article focuses on Afghan women's courage in resisting physical and other violence and victimization through their writings. It argues that the absence of a strong Afghan female voice has led numerous female writers to highlight women's issues in Afghanistan. It demonstrates the courage and gradual awakening of women in Afghanistan to fight against violence and victimization in a culturally complex and patriarchal society. Thus, this is an appraisal of their struggle and highlights women's issues in order to spread awareness about gaining a voice by women being vital for survival. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR-T) cell therapy has been applied successfully in treating hematologic malignancies; however, it shows very limited efficacy in treating solid tumors. Adenosine is one of the key immunosuppressive metabolites in tumor microenvironment (TME) of solid tumors. Although the effect of adenosine has been well studied using mouse CAR-T cells, its effect on human CAR-T cells has not been fully elucidated. In particular, there was no evaluation of the CAR-T cells with blocked adenosine signaling in tumor xenograft animal model, which is essential for determining the feasibility of future clinical trials. In this study, we found the expression of A2a receptor (A2AR) and A2b receptor (A2BR) both upregulated in human-derived CAR-T cells, and only A2AR was responsible for adenosine-induced impairment of CAR-T cell function. Disrupting A2AR gene in human CAR-T cells with CRISPR-Cas9 increased the anti-tumor function and prevented the exhaustion of CAR-T cells in vitro. Furthermore, CRL5826-CDX model and two patient-derived xenograft solid tumor models were applied to evaluate the efficacy of A2AR knock-out CAR-T cells, which showed superior capability of inhibiting tumor growth. Taken together, these results demonstrate that A2AR knock-out CAR-T cells have the potential of being an improved CAR-T cell therapy in treating solid tumors. [ABSTRACT FROM AUTHOR]

Taxifolin is a potent flavonoid with anti-inflammatory activity. Taxifolin has been reported to decrease the accumulation of β-amyloid (Aβ), and reduce Aβ-induced neurotoxicity. However, the detail molecular mechanism of taxifolin against Aβ-induced neurotoxicity is largely unknown. In this study, we revealed the protective effects and the underlying mechanisms of taxifolin on the impairments of cognitive function and synapse formation induced by soluble Aβ oligomers. Our results showed that taxifolin prevented neuronal cell death in a concentration-dependent manner. The recognition memory in novel object recognition tasks and the spatial memory in Morris water maze tests are significantly lower in the Alzheimer’s disease (AD) model mice induced by hippocampal injection of Aβ42. Taxifolin treatment prevented the recognitive and spatial memory deficits of the AD mice. 10 mg/kg taxifolin treatment also significantly prevented the decreased expression levels of PSD 95 induced by Aβ42. Live cell imaging study showed that 2 h pre-treatment of taxifolin prevented the decrease in the number of filopodium and spine induced by Aβ42 oligomers. Aβ42 oligomers significantly increased the production of cytosolic phospholipase A2 (cPLA2), a crucial enzyme of pro-inflammatory mediator, and prostaglandin E2 (PGE2), a neuroinflammatory molecule. Taxifolin significantly reduced the content of cPLA2 and PGE2 induced by Aβ42 both in the primary hippocampal neurons and hippocampal tissues. These results indicated that taxifolin might prevent Aβ42 oligomer-induced synapse and cognitive impairments through decreasing cPLA2 and PGE2. Our study provided novel insights into the cellular mechanisms for the protective effects of taxifolin on AD. [ABSTRACT FROM AUTHOR]

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of Tcell activity is lymphocyte activation gene-3 ( LAG-3). We successfully generated LAG-3 knockout Tand CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture. LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model, which is comparable to standard CAR-T cells. Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing. [ABSTRACT FROM AUTHOR]

Multiple primary cancers (MPCs) have an increasing incidence rate due to the detection of early stages of cancer and the development of effective therapeutic strategies. MPCs are less common compared with metachronous cancers. Therefore, distinguishing synchronous primary tumors from metastasis and developing an individualized treatment strategy can be challenging. In the present study, the case of a 70-year-old female who was referred to The First Hospital of Jilin University (Changchun, China) with an enlarged left cervical lymph node and no other clinical manifestations is reported. Radiography revealed distinct lesions in the left breast, left cervical lymph node and bilateral lungs. Subsequently, a biopsy was performed in all three lesions and then each specimen was subjected to immunohistochemistry, fluorescence in situ hybridization, amplification refractory mutation system-PCR and next-generation sequencing (NGS). Disease-related enrichment of lymph node mutant genes and Gene Ontology Biological Process enrichment of breast, as well as lung, mutant genes were performed using the Database for Annotation, Visualization and Integrated Discovery. Based on the molecular assessment, the patient was finally diagnosed with breast invasive ductal carcinoma, primary lung adenocarcinoma and cervical lymph node metastatic lung adenocarcinoma. Since primary synchronous breast and lung cancer (SBLC) is rare, a molecular assessment, particularly using NGS, could provide important information for both the diagnosis and treatment of SBLC. [ABSTRACT FROM AUTHOR]

Objective: To determine effects of Whole Body Vibration Exercise (WBVE) associated with quadriceps resistance exercises (QRE) versus QRE only on pain, physical function, biomarkers in serum and urine, activities of daily living (ADL), and quality of life in patients with knee osteoarthitis (OA). Design: Randomized-controlled trial . Setting: Rehabilitation medicine outpatient department of West China Hospital, Chengdu, Sichuan, People’s Republic of China. Subjects: Forty-nine patients were assigned to WBVE+QRE and 50 to QRE . Main outcome measures: Primary outcomes included pain assessed with visual analogue scale (VAS), Timed up & go test (TUG), 6-min walk distance test (6MWD), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes comprised range of motion, muscular strength, serum COMP and urinary CTX-II, Lequesne Index (LI), and SF-36. All outcomes were analyzed with mixed effects regression. Results: Compared with QRE, WBVE+QRE showed significantly greater improvement in VAS at 4weeks (p=0.03), in VAS (p<0.01), 6MWD (p=0.01), WOMAC pain (p=0.01), and WOMAC physical function (p=0.02) at 16 weeks, and in all primary outcomes at 24 weeks (all p<0.01). Conclusion: Over a six months period, WBVE in combination with QRE was superior to QRE in most outcomes. [ABSTRACT FROM AUTHOR]

Bis(propyl)-cognitin (B3C), derived from tacrine linked with three methylene (-CH2-) groups, is a dimerized molecule interacting multiple targets. During the past several years, it has been reported as a promising therapeutic drug for Alzheimer's disease (AD) and other neurodegenerative disorders. However, the therapeutic mechanism of B3C for AD needs further demonstration. Based on a combination of behavioral tests, electrophysiological technique, immunocytochemistry, and live cell imaging, we studied the effects and the underlying mechanism of B3C on the impairments of cognitive function, synapse formation, and synaptic plasticity induced by soluble amyloid-β protein (Aβ) oligomers. Our study showed that spatial learning and memory in a Morris water maze task and recognition memory in a novel object recognition task were significantly decreased in the AD model mice created by hippocampal injection of Aβ. Chronic administration of B3C for 21 days prevented the memory impairments of the AD model mice in a dose-dependent manner. Live cell imaging study showed that 2-h pretreatment of B3C prevented the decrease in the number of filopodia and synapses induced by Aβ (0.5 μM) in a dose-dependent manner. Besides, electrophysiological recording data showed that the inhibition of long-term potentiation (LTP) induced by Aβ oligomers in the dentate gyrus (DG) of hippocampus was prevented by B3C in a dose-dependent manner. Furthermore, we found that the neuroprotective effect of B3C against Aβ-oligomer-induced impairments of synaptic formation and plasticity could be partially blocked by a specific phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 (50 μM). Therefore, these results indicate that B3C can prevent Aβ-oligomer-induced cognitive deficits, synaptic formation impairments, and synaptic plasticity impairments in a concentration-dependent manner. These effects of B3C are partially mediated via the PI3-K pathway. This study provides novel insights into the cellular mechanisms for the protective effects of B3C on AD. [ABSTRACT FROM AUTHOR]

Roles of ionotropic purinergic (P2X) receptors in chronic pain have been intensively investigated. However, the contribution of metabotropic purinergic (P2Y) receptors to pathological pain is controversial. In the present study, using single cell RT-PCR (reverse transcription-polymerase chain reaction) and single cell nested-PCR techniques, we examined the expression of P2X, P2X, P2Y and P2Y mRNA transcripts in retrogradely labeled cutaneous sensory neurons from mouse lumber dorsal root ganglia (DRGs) following peripheral inflammation. The percentage of cutaneous sensory neurons expressing P2Y mRNA transcripts increased after complete Freund's adjuvant (CFA) treatment. Particularly, the P2Y mRNA transcripts were more frequently detected in small-diameter cutaneous neurons from CFA-treated mice than those from control mice. Coexpression of P2Y and P2X (P2X or P2X) mRNAs was more frequently observed in cutaneous sensory neurons from CFA-treated mice relative to controls. Pain behavioral tests showed that the blockade of P2Y receptors by suramin attenuated mechanical allodynia evoked either by CFA or uridine triphosphate (UTP), an endogenous P2Y and P2Y agonist. These results suggest that chronic inflammatory pain enhances expression of P2Y receptor in peripheral sensory neurons that innervate the injured tissue and the activation of P2Y receptors contributes to mechanical allodynia following inflammation. [ABSTRACT FROM AUTHOR]

Small proline-rich repeat protein 1A (SPRR1A) is a marker for terminal squamous cell differentiation. Previous studies showed that SPRR1A expression increases in squamous cell carcinoma of the skin, but decreases in esophageal squamous cell carcinoma. This study focuses on the expression of SPRR1A protein in breast cancers (BCs) in China. A total of 111 patients with histologically confirmed BC, who underwent radical surgery between January 2006 and September 2007 in China Medical University, were enrolled. The relationship between SPRR1A expression and clinicopathological factors as well as BC prognoses was also determined. Overall, SPRR1A expression was detected in more than half of the BC specimens by immunohistochemistry (56/111, 53.8 %), but there was no significant difference between age groups (≥50 vs. <50 years) in terms of SPRR1A expression ( P = 0.915), as well as no differences between SPRR1A expression and the clinical stage (0-I vs. II-III) or nodal status ( P = 0.234 and 0.632, respectively). Moreover, human epidermal growth factor receptor 2 overexpression was not correlated with SPRR1A expression, whereas Ki67 was associated with SPRR1A expression ( P = 0.155 and 0.028, respectively). Interestingly, SPRR1A expression was significantly associated with progesterone receptor-positive ( P = 0.010) rather than estrogen receptor-positive (0.778) BCs. The 5-year survival rate in patients did not differ with the presence or absence of SPRR1A expression ( P = 0.753), whereas the combination of SPRR1A expression, progesterone receptor status, and menopausal status allowed identification of a subgroup of BC patients with a good long-term prognosis. Thus, the SPRR1A status might play an important role in the prognosis of postmenopausal breast carcinoma patients, especially that of progesterone receptor-positive subgroups. [ABSTRACT FROM AUTHOR]

A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)-TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2′-deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by1H-NMR,31P-NMR, and HRMS with purity of up to 99%. The synthesized dye-labeled terminator incorporated into DNA strand successfully, and the fluorophore was cleaved completely under acidic conditions. The preliminary results encourage us to explore more acid-sensitive linkers for DNA SBS to increase the cleavage efficiency under weakly acidic conditions. [ABSTRACT FROM PUBLISHER]

The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on short-term and long-term joint pain, synovitis, anabolic, and catabolic factors in the cartilage of a rabbit model with progressive osteoarthritis (OA) induced by anterior cruciate ligament transection (ACLT). A total of 160 New Zealand white rabbits were randomly assigned into two groups (ACLT group and LLLT group). All rabbits received ACLT surgery, and 2-, 4-, 6-, and 8-week treatment after the surgery, with 20 rabbits being tested biweekly over every study period. The LLLT group received LLLT with a helium-neon (He-Ne) laser (830 nm) of 1.5 J/cm three times per week, and the ACLT group received placebo LLLT with the equipment switched off. Long-term and short-term pain was tested via weight-bearing asymmetry; synovitis was assessed histologically; and knee joint cartilage was evaluated by gross morphology, histology, and gene expression analysis of anabolic and catabolic factors. The histological assessment of pain and synovitis showed that at least 6-week intermittent irradiation of LLLT could relief knee pain and control synovium inflammation. Gross morphologic inspection and histological evaluation showed that 6 weeks of LLLT could decrease cartilage damage of medical femoral condyle and 8 weeks of LLLT could decrease cartilage damage of medical and lateral femoral condyles and medical tibial plateau. Gene expression analysis revealed two results: At least 6 weeks of LLLT could decrease production of catabolic factors, for example, interleukin 1β (IL-1β), inducible nitric oxide synthase (iNOS), and MMP-3, and slow down the loss of anabolic factors, mainly TIMP-1. Eight weeks of LLLT treatment could slow down the loss of collagen II, aggrecan, and anabolic factors, mainly transforming growth factor beta (TGF-β). The study suggests that LLLT plays a protective role against cartilage degradation and synovitis in rabbits with progressive OA by virtue of the regulation of catabolic and anabolic factors in the cartilage. [ABSTRACT FROM AUTHOR]

Multipath routing has been considered as one of the most efficient and reliable routing solutions for ad hoc networks. Compared with the link-disjoint paths, the node-disjoint paths are less likely to fail and provide better performance for load balancing. In this paper, a novel multipath routing protocol called BGM (Beacon-less Geographic Multipath routing protocol) is proposed to construct maximally node-disjoint multiple paths. Unlike most existing multipath routing protocols based on AODV or DSR, the proposed geographic routing algorithm utilizes location information to discover multiple paths. Therefore it avoids lots of control messages caused by route discovery and maintenance in the topology-based protocols. In the proposed scheme, each node discovers multiple paths and forwards data packets within a disjoint sub-zone divided by a division algorithm. Moreover, in order to reduce the control overhead, a distributed forwarding strategy is presented by applying the beacon-less mechanism. The beacon-less mechanism does not require nodes to periodically broadcast the Hello messages. Instead, the neighbors of a forwarding node contend to deliver data packets. Simulation results show that BGM not only improves the efficiency of the path discovery, but also reduces the control overhead. Also, BGM provides relatively short end-to-end delay while keeping the packet delivery ratio above 95 %. [ABSTRACT FROM AUTHOR]

Background: Currently, a constant shortage in the supply of platelets has become an important medical and society challenge, especially in developing country, and the in vitro production of megakaryocytic progenitor cells (MPs) from cord blood could represent an effective platelet substitute. In the present study, our objective was to determine the safety and feasibility of ex vivo generated MPs in patients. Methods and Findings: MPs were produced and characterized from cord blood mononuclear cells under a serum free medium with cytokines. We investigated the feasibility of expansion and infusion of cord blood-derived MPs in 24 patients with advanced hematological malignancyes. The primary end point was the safety and tolerability of the infusion of cord blood-derived MPs. No adverse effects were observed in patients who received ex vivo-generated cells at concentrations of up to a median value of 5.45×106cells/kg of body weight. With one year follow-up, acute and chronic GVHD had not been observed among patients who received MPs infusion, even without ABO blood group and HLA typing matching. Conclusions: These initial results in patients are very encouraging. They suggest that infusion of cord blood-derived MPs appears safe and feasible for treatment of thrombocytopenia. Trial Registration: www.chictr.org ChiCTR-TCH-09000333. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that controls vascular responses to hypoxia and ischemia. In this study, mice that were heterozygous (HET) for a null allele at the locus encoding the HIF-1α subunit (HET mice) and their wild-type (WT) littermates were subjected to a thermal injury involving 10% of the body surface area. HIF-1α protein levels were increased in burn wounds of WT but not of HET mice on day 2. The serum levels of stromal-derived factor 1α, which binds to CXCR4, were increased on day 2 in WT but not in HET mice. Circulating angiogenic cells were also increased on day 2 in WT but not in HET mice and included CXCR4+Sca1+ cells. Laser Doppler perfusion imaging demonstrated increased blood flow in burn wounds of WT but not HET mice on day 7. Immunohistochemistry on day 7 revealed a reduced number of CD31+ vessels at the healing margin of burn wounds in HET as compared with WT mice. Vessel maturation was also impaired in wounds of HET mice as determined by the number of α-smooth muscle actin-positive vessels on day 21. The remaining wound area on day 14 was significantly increased in HET mice compared with WT littermates. The percentage of healed wounds on day 14 was significantly decreased in HET mice. These data delineate a signaling pathway by which HIF-1 promotes angiogenesis during burn wound healing. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal stromal tumors (GISTs), a type of mesenchymal tumor in the gastrointestinal tract, are believed to be closely associated with PDGFRA and C-KIT mutations. Schwannoma in the stomach, which is an unusual location, is a rare disorder. The simultaneous occurrence of the two diseases is rarer than metachronous occurrences, and its pathological characteristics have not been reported to date. We present a case report on a patient with simultaneous coexistence of gastric schwannoma and GISTs. Case presentation: A 39-year-old female visited our hospital complaining of intermittent abdominal pain for the previous 3 months. CT revealed a 3.4 cm slight homogeneous enhancement in the lesser curvature of the stomach; the mass was nodular soft tissue, which was removed by radical surgery. Two solid tumors with different volumes were located in the stomach. Histologically and immunohistochemically different, the larger tumor consisted of spindle cells surrounded by a peripheral lymphoid cuff, and was positive for S-100. The larger tumor was therefore classified as a gastric schwannoma. The smaller tumor was composed of medium-sized round, oval cells with amphiphilic granular cytoplasm; vacuolization was also observed. The tumor cells were positive for DOG1 and sporadically positive for CD34 and CD117. Hence, the smaller tumor was diagnosed as epithelioid GISTs. Sanger sequencing revealed that the GIST tumor cells contained a deletion mutation (c.2527_2538 del12,843–846del4), which was located in exon 18 of PDGFRA. Conclusion: GISTs combined with gastric schwannoma are a considerably rare subgroup of gastric tumors. Related clinical research is comparatively weak, and the mechanism remains unknown. We reviewed related articles to provide knowledge to improve the correct identification, diagnosis and management of patients with gastric cancer. All pathologists involved in the diagnosis and clinicians involved in the treatment should be aware of this new kind of disease pattern to improve their understanding of the disease. [ABSTRACT FROM AUTHOR]