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Abstract Cognitive impairment is a common issue among human patients undergoing surgery, yet the neural mechanism causing this impairment remains unidentified. Surgical procedures often lead to glial cell activation and neuronal hypoexcitability, both of which are known to contribute to postoperative cognitive dysfunction (POCD). However, the role of neuron-glia crosstalk in the pathology of POCD is still unclear. Through integrated transcriptomics and proteomics analyses, we found that the complement cascades and microglial phagocytotic signaling pathways are activated in a mouse model of POCD. Following surgery, there is a significant increase in the presence of complement C3, but not C1q, in conjunction with presynaptic elements. This triggers a reduction in excitatory synapses, a decline in excitatory synaptic transmission, and subsequent memory deficits in the mouse model. By genetically knockout out C3ar1 or inhibiting p-STAT3 signaling, we successfully prevented neuronal hypoexcitability and alleviated cognitive impairment in the mouse model. Therefore, targeting the C3aR and downstream p-STAT3 signaling pathways could serve as potential therapeutic approaches for mitigating POCD.

Summary: Motivated by the cellular heterogeneity in complex tissues, particularly in brain and induced pluripotent stem cell (iPSC)-derived brain models, we developed a complete workflow to reproducibly characterize cell types in complex tissues. Our approach combines a flow cytometry (FC) antibody panel with our computational pipeline CelltypeR, enabling dataset aligning, unsupervised clustering optimization, cell type annotating, and statistical comparisons. Applied to human iPSC derived midbrain organoids, it successfully identified the major brain cell types. We performed fluorescence-activated cell sorting of CelltypeR-defined astrocytes, radial glia, and neurons, exploring transcriptional states by single-cell RNA sequencing. Among the sorted neurons, we identified subgroups of dopamine neurons: one reminiscent of substantia nigra cells most vulnerable in Parkinson’s disease. Finally, we used our workflow to track cell types across a time course of organoid differentiation. Overall, our adaptable analysis framework provides a generalizable method for reproducibly identifying cell types across FC datasets in complex tissues.

Abstract Tantalum and aluminum on sapphire are widely used platforms for qubits of long coherent time. As quantum chips scale up, the number of Josephson junctions on sapphire increases. Thus, both the uniformity and stability of the junctions are crucial to quantum devices, such as scalable superconducting quantum computer circuit, and quantum-limited amplifiers. By optimizing the fabrication process, especially, the conductive layer during the electron beam lithography process, Al/AlOx/Al junctions of sizes ranging from 0.0169 to 0.04 µm2 on sapphire substrates were prepared. The relative standard deviation of room temperature resistances (R N) – $${\upsigma }_{{R_{{\text{N}}} }} /\left\langle {R_{{\text{N}}} } \right\rangle$$ σ R N / R N of these junctions is better than 1.7% on 15 mm × 15 mm chips, and better than 2.66% on 2 inch wafers, which is the highest uniformity on sapphire substrates has been reported. The junctions are robust and stable in resistances as temperature changes. The resistances increase by the ratio of 9.73% relative to R N as the temperature ramp down to 4 K, and restore their initial values in the reverse process as the temperature ramps back to room temperature. After being stored in a nitrogen cabinet for 100 days, the resistance of the junctions changed by1.16% on average. The demonstration of uniform and stable Josephson junctions in large area paves the way for the fabrication of superconducting chip of hundreds of qubits on sapphire substrates.

PurposeTo investigate the effects of various intervention approaches on cancer-related fatigue (CRF) in patients with breast cancer.MethodComputer searches were conducted on PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang databases from their establishment to June 2023. Selection was made using inclusion and exclusion criteria, and 77 articles were included to compare the effects of 12 interventions on patients with breast cancer.ResultsSeventy-seven studies with 12 various interventions were examined. The network findings indicated that cognitive behavioral therapy (CBT) (SMD, -1.56; 95%CI, -3.08~-0.04), Chinese traditional exercises (CTE) (SMD, -0.85; 95%CI, -1.34~-0.36), aerobic exercise (AE) (SMD, -0.77; 95%CI, -1.09~-0.45), multimodal exercise (ME) (SMD, -0.75; 95%CI, -1.26~-0.25), music interventions (MI) (SMD, -0.74; 95%CI, -1.45~-0.03), and yoga (YG) (SMD, -0.44; 95%CI, -0.83 to -0.06) can reduce CRF more than the control group (CG). For relaxation exercises (RE) (MD, -6.69; 95%CI, -9.81~-3.57), MI (MD, -5.45; 95%CI, -7.98~-2.92), AE (MD, -4.34; 95%CI, -5.90~-2.78), ME (MD, -3.47; 95%CI, -4.95~-1.99), YG (MD, -2.07; 95%CI, -3.56~-0.57), and mindfulness training (MD, -1.68; 95%CI, -2.91~-0.46), PSQI improvement was superior to CG. In addition, for CTE (MD, 11.39; 95%CI, 4.11-18.66), YG (MD, 11.28; 95%CI, 1.63-20.93), and AE (MD, 9.34; 95%CI, 0.26~18.42), Functional Assessment of Cancer Therapy-Breast improvement was superior to CG.ConclusionCognitive behavioral therapy (CBT) is the most effective measure for alleviating CRF in patients with breast cancer and Relaxation exercises (RE) is the most effective measure for improving sleep quality. In addition, Chinese traditional exercises (CTE) is the best measure for enhancing quality of life. Additional randomized controlled trials (RCTs) are expected to further investigate the efficacy and mechanisms of these interventions.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023471574.

There has been a huge discrepancy between the vacuum energy density calculated based on the existing quantum theories and the observational values. The calculated vacuum energy density is about 120 orders of magnitude greater than its observational values, which is one of the worst theoretical predictions in the history of modern physics. As a promising quantum gravity theory, the newly developed fractal quantum gravity (FQG) theory has introduced the smallest constant of the product of space, time and energy of Space-Time Quantum of Action (STQA). The product of space, time and energy of every particle is integer times of this smallest constant — STQA. Based on the FQG equation, we have calculated the vacuum energy density which is a perfect match with its observational values. This recent development has shed much insight into the intrinsic nature of vacuum and it will continue to provide guidance of future research in the area of dark energy.

The porous-medium approximation (PM) approach is extensively employed in large-quantity grid simulations of heat exchangers, providing a time-saving approach in engineering applications. To further investigate the influence of different geometries on the implementation of the PM approach, we reviewed existing experimental conditions and performed numerical simulations on both straight fins and serrated fins. Equivalent flow and heat-transfer factors were obtained from the actual model, and computational errors in flow and heat transfer were compared between the actual model and its PM model counterpart. This exploration involved parameters such as aspect ratio (a*), specific surface area (Asf), and porosity (γ) to evaluate the influence of various geometric structures on the PM approach. Whether in laminar or turbulent-flow regimes, when the aspect ratio a* of straight fins is 0.98, the flow error (δf) utilizing the PM approach exceeds 45%, while the error remains within 5% when a* is 0.05. Similarly, for serrated fins, the flow error peaks (δf > 25%) at higher aspect ratios (a* = 0.61) with the PM method and reaches a minimum (δf < 5%) at lower aspect ratios (a* = 0.19). Under the same Reynolds numbers (Re), employing the PM approach results in an increased heat-transfer error (δh)with rising porosity (γ) and decreasing specific surface area (Asf), both of which remained under 10% within the range of this study. At lower aspect ratios (a*), the fin structure becomes more compact, resulting in a larger specific surface area (Asf) and smaller porosity (γ). This promotes more uniform flow and heat transfer within the model, which is closer to the characteristics of PM. In summary, for straight fins at 0 < a* < 0.17 in the laminar regime (200 < Re < 1000) and in the turbulent regime (1200 < Re < 5000) and for serrated fins at 0 < a* < 0.28 in the laminar regime (400 < Re < 1000) or 0 < a* < 0.32, in the turbulent regime (2000 < Re < 5000), the flow and heat-transfer errors are less than 15%.

Nerves within bone play an irreplaceable role in promoting bone regeneration. Crosstalk between the nerve system and bone has arisen to the attention of researchers in the field of basic medicine, clinical medicine, and biomaterials science. Successful bone regeneration relies on the appropriate participation of neural system components including nerve fibers, signaling molecules, and neural-related cells. Furthermore, more about the mechanisms through which nerves took part in bone regeneration and how these mechanisms could be integrated into tissue engineering scaffolds were under exploration. In the present review, we aimed to systematically elaborate on the structural and functional interrelationship between the nerve system and bone. In particular, peripheral nerves interact with the bone through innervated axons, multiple neurotrophins, and bone resident cells. Also, we aimed to summarize research that took advantage of the neuro-osteogenic network to design tissue engineering scaffolds for bone repair.

Based on the smallest physical constant of the product of space interval, time interval, and energy, the fractal quantum gravity (FQG) theory has demonstrated that every particle or physical system consists of these smallest units in fractal structures. The general relativity is an approximation of the FQG equation when the quantum effect is negligible, while the quantum theory is an approximation of the FQG equation when the interaction between space, time, and energy is very weak or negligible. The stationary-action principle can be derived from the FQG equation. The mass range of possibly existing elementary particles and an accelerating expansion evolution model of the universe can be obtained through the FQG equation. This FQG equation satisfied almost all the requirements of a quantum gravity theory and there is no free constant needed in the FQG theory. It looks promising that the FQG theory may offer a novel way to calculate all the free constants in the Standard Model of particle physics and general relativity.

Tyrosine-decahydrofluorene derivatives feature a fused [6.5.6] tricarbocyclic core and a 13-membered para-cyclophane ether. Herein, we identified new xenoacremones A, B, and C (1−3) from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus nidulans. The hybrid polyketide synthase–nonribosomal peptide synthetase (PKS−NRPS) XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide skeleton. This skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone moiety. XenF catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring system. Subsequent oxidation catalyzed by XenD supplied the substrate for XenC to link the para-cyclophane ether, which underwent subsequent spontaneous Diels−Alder reaction to give the end products. Thus, the results indicated that three novel enzymes XenF, XenD, and XenC coordinate to assemble the [6.5.6] tricarbocyclic ring and para-cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives.

Abstract Background This study was conducted to evaluate the impact of a comprehensive community intervention on cognition and inoculation behaviors of diabetic patients immunized with influenza vaccine. Methods A total of 1538 diabetic patients aged 35 years and above for outpatient visits and follow-up treatments were selected from six community health service centers (three for the experimental group, and the other three for the control group) in Chaoyang District, Beijing. Comprehensive interventions applied to the experimental group include patient intervention and community climate interventions. We compared the total awareness of influenza vaccine knowledge and influenza vaccination rates between the two groups before and after the intervention. Results Before the intervention, the total awareness rate of influenza vaccine in the experimental group and the control group was similar (50.6 and 50.2%, respectively. P = 0.171). After the intervention, the awareness rate of influenza vaccine in the experimental group and the control group increased. The amplitude of the increase was similar (70.3 and 70.1%, respectively. P = 0.822,). Before the intervention, there was no significant difference in the influenza vaccination rate between the experimental group and the control group (29.0 and 26.8%, respectively. P = 0.334). After the intervention, the vaccination rate of the experimental group was higher than that of the control group. The difference was statistically significant (The vaccination rate 45.8 and 27.4% for the experimental group and the control group, respectively. P

To continuously monitor the discharge of the Yangtze River, two coastal acoustic tomography (CAT) systems with synchronized transmission were deployed at the Datong hydrometric station of the Yangtze River from July 2018 to January 2021. To accurately estimate the discharge of the Yangtze River, the cross-sectional averaged flow velocity and area data were estimated by establishing two empirical relationships: one between the range-averaged flow velocity measured by acoustic Doppler current profiler (ADCP) and the reciprocal travel time difference measured by CAT, and the other between the ADCP-measured cross-sectional area and the water-surface elevation (stage). Compared with the discharges directly measured by ADCP, our estimation had the root mean square error of 946 m3/s, accounting for 2.5% of the mean discharge. The discharges varied from 10,981 to 81,807 m3/s over the 2.5-years observational period, with a mean of 30,708 m3/s. The annual mean discharge was 29,163 and 34,763 m3/s in 2019 and 2020, respectively. Our monitoring successfully covered two complete flood processes, with a peak discharge of 69,744 (July 17, 2019) and 81,807 m3/s (July 13, 2020). Our study provides an innovative method to achieve accuracy and real-time monitoring of river discharges even during extreme flood events.

The persistence of immunity after hepatitis B vaccination is still under investigation in adults. In Chaoyang District, Beijing, people who were aged ≥ 18 years and completely immunized with HBV vaccine according to the standard procedure (0–1–6 months) were enrolled. Three groups were set for 1 (Y1), 5 (Y5) and 10 (Y10) years after the hepatitis B vaccination. The following data was collected and analyzed: antibody against hepatitis B virus surface antigen(anti-HBs) positive rates and geometric mean concentration (GMC) between the different compared groups through questionnaires and laboratory detection, including hepatitis B virus surface antigen (HBsAg), anti-HBs and antibody against hepatitis B virus core antigen(anti-HBc). All 600 subjects completed the questionnaires and serological tests. Among all subjects, the positive rates of HBsAg, anti-HBs and anti-HBc were 0, 70.5% (423/600) and 2.5% (15/600), respectively. The anti-HBs positive rates in Y1, Y5 and Y10 groups were 86.5% (173/200), 71.0% (142/200) and 54.0% (108/200) (χ2 = 50.8, p < 0.001) and showed a linear decreasing trend year by year (trend χ2 = 50.7, p < 0.001). The GMC in Y1, Y5 and Y10 groups were 296.6 mIU/mL, 51.6 mIU/mL and 25.5 mIU/mL (H = 64.8, p < 0.001), respectively. The anti-HBs positive rates and GMC decreased rapidly after the vaccination of adults against hepatitis B. Screening after 5–10 years and booster vaccination for the unprotected population is recommended.

Abstract Background Condom use and antiretroviral therapy (ART) are effective means to prevent and control HIV transmission. We aimed to assess the effect of condom use in combination with antiretroviral therapy (ART) on HIV incidence and mortality among men who had sex with men (MSM) in Beijing, China. Methods We evaluated the effect of condom use, ART, and the combination of both among people living with HIV/AIDS (PLWHA) of MSM in the Chaoyang District of Beijing using the Asian Epidemic Model (AEM). Evaluation indicators included absolute risk reduction (ARR) and the percentage of relative risk reduction (RRR %). Results HIV incidence and prevalence declined substantially when condoms were used by MSM in Chaoyang from 2003 to 2013. The ARR of HIV incidence was from 0 to 0.91% and the RRR% was from 0 to 43.93%. The ARR of HIV prevalence was from 0 to 3.79% and the RRR% was from 0 to 31.53%. The HIV mortality rate decreased substantially (ARR from 0 to 1.75%, and RRR% from 0 to 40.03%) when ART was implemented. When condom use combined with ART was implemented in MSM in 2003–2013, HIV incidence declined substantially (ARR from 0 to 0.99%, and RRR% from 0 to 46.11%). HIV prevalence was also reduced with an ARR from 0 to 3.5%, and an RRR% from 0 to 29.88%. The HIV mortality also declined substantially (ARR from − 0.01% to 1.02%, RRR% from − 1.44% to 39.98%). Conclusions Among MSM, a combination of condom use and ART reduces both HIV incidence and mortality caused by HIV. Combining these methods results in a more effective prevention and control of HIV.

Masonry structures without effective reinforcement are vulnerable to seismic excitation. An innovative strengthening technique was proposed for damaged and undamaged masonry walls. Six confined masonry units with two aspect ratios were tested under in-plane lateral cyclic loading, which consisted of two control walls, two original walls strengthened with reactive powder concrete (RPC-1), and two damaged walls repaired with RPC (RPC-2). The results of the specimens retrofitted with RPC demonstrated that the proposed technique significantly enhanced the seismic performance of masonry walls in terms of lateral strength, ductility, and energy dissipation. Furthermore, the two repaired specimens had a better distributed cracking pattern than the two strengthened specimens. The analysis of the results leads to a better understanding of the effect and mechanism of RPC seismic retrofitting for confined masonry walls.

Chronic neck pain is a highly prevalent condition, and is often treated with non-steroidal anti-inflammatory drugs. Limited clinical studies with short-term follow-up have shown promising efficacy of acupuncture as well as miniscalpel-needle (MSN) release. In this retrospective study, we examined whether MSN release could produce long-lasting relief in patients with chronic neck pain.We retrieved the medical records of all patients receiving weekly MSN release treatment for chronic neck pain at this institution during a period from May 2012 to December 2013. Only cases with the following information at prior to, and 1, 6, and 12 months after the treatment, were included in the analysis: neck disability index (NDI), numerical pain rating scale (NPRS), and active cervical range of motion (CROM). The primary analysis of interest is comparison of the 12-month measures with the baseline. Patients who took analgesic drugs or massage within 2 weeks prior to assessment were excluded from the analysis. For MSN release, tender points were identified manually by an experienced physician, and did not necessarily follow the traditional acupuncture system. MSN was inserted vertically (parallel to the spine) until breaking through resistance and patient reporting of distention, soreness or heaviness. The depth of the needling ranged from 10 to 50 mm. The release was carried out by moving the MSN up and down 3-5 times without rotation.A total of 559 cases (patients receiving weekly MSN release treatment for chronic neck pain) were screened. The number of cases with complete information (NDI, NPRS, and CROM at baseline, 1, 6 and 12 months after last treatment) was 180. After excluding the cases with analgesic treatment or massage within 2 weeks of assessment (n = 53), a total of 127 cases were included in data analysis. The number of MSN release session was 7 (range: 4-11). At 12 months after the treatment, both NPRS and NDI were significantly lower [3 (0, 9) vs. 7 (5, 10) at the baseline for NPRS; [7 (0, 21) vs. 17 (9, 36) for NDI; p

OBJECTIVE: We investigated the awareness and acceptability of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and potential predicting factors. METHODS: This study was conducted among MSM in Beijing, China. Study participants, randomly selected from an MSM cohort, completed a structured questionnaire, and provided their blood samples to test for HIV infection and syphilis. Univariate logistic regression analyses were performed to evaluate the factors associated with willingness to accept (WTA) PrEP. Factors independently associated with willingness to accept were identified by entering variables into stepwise logistic regression analysis. RESULTS: A total of 152 MSM completed the survey; 11.2% had ever heard of PrEP and 67.8% were willing to accept it. Univariate analysis showed that age, years of education, consistent condom use in the past 6 months, heterosexual behavior in the past 6 months, having ever heard of PrEP and the side effects of antiretroviral drugs, and worry about antiretroviral drugs cost were significantly associated with willingness to accept PrEP. In the multivariate logistic regression model, only consistent condom use in the past 6 months (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.13-0.70) and having ever heard of the side effects of antiretroviral drugs (OR: 0.30; 95% CI: 0.14-0.67) were independently associated with willingness to accept PrEP. CONCLUSIONS: The awareness of PrEP in the MSM population was low. Sexual behavioral characteristics and knowledge about ART drugs may have effects on willingness to accept PrEP. Comprehensive prevention strategies should be recommended in the MSM community.

The frequency domain analysis (FDA) offers greater computational efficiency than the method of characteristic (MOC) in simulating transient flow in pressurized pipes. However, its accuracy is hindered by linearisation errors. Violations of the assumptions for linearisation in friction term and valve equations during water distribution systems (WDSs) burst simulations make the FDA results meaningless. Linearisation procedures are modified as follows using the Heaviside property of pipeline bursts to address this problem: (1) the linearization of the friction term is adjusted, and (2) the valve equation is approximated using a three-step approach. The higher-order term dropped by the original FDA is linearly approximated to achieve better accuracy. The modified FDA is compared to the MOC in a real-life WDS by numerical experiment. Excellent precision can be observed even for a highly nonlinear case where the burst flow is 20% of the initial total demand. The simulation time is significantly shorter than when using the MOC. The proposed modification dramatically improves the applicability of the FDA for solving the nonlinear error issue during the simulation of the pipeline burst. This result implies the potential for its application in quick inverse analysis of pipeline bursts.