Hyperexcitability precedes CA3 hippocampal neurodegeneration in a dox-regulatable TDP-43 mouse model of ALS-FTD.

Neuronal hyperexcitability is a hallmark of amyotrophic lateral sclerosis (ALS) but its relationship with the TDP-43 aggregates that comprise the predominant pathology in over 90% of ALS cases remains unclear. Emerging evidence in tissue and slice culture models indicate that TDP-43 pathology induces neuronal hyperexcitability suggesting it may be responsible for the excitotoxicity long believed to be a major driver of ALS neuron death. Here, we characterized hyperexcitability and neurodegeneration in the hippocampus of doxycycline-regulatable rNLS8 mice (NEFH-tTA x tetO-hTDP-43ΔNLS), followed by treatment with AAV encoded DREADDs and anti-seizure medications to measure the effect on behavioral function and neurodegeneration. We found that approximately half of the CA3 neurons in the dorsal hippocampus are lost between 4 and 6 weeks after TDP-43ΔNLS induction. Neurodegeneration was preceded by selective hyperexcitability in the mossy fiber - CA3 circuit, leading us to hypothesize that glutamate excitotoxicity may be a significant contributor to neurodegeneration in this model. Interestingly, hippocampal injection of AAV encoded inhibitory DREADDs (hM4Di) and daily activation with CNO ligand rescued anxiety deficits on elevated zero maze (EZM) but did not reduce neurodegeneration. Therapeutic doses of the anti-seizure medications, valproic acid and levetiracetam, did not improve behavior or prevent neurodegeneration. These results highlight the complexity of TDP-43 - induced alterations to neuronal excitability and suggest that whereas targeting hyperexcitability can meliorate some behavioral deficits, it may not be sufficient to halt or slow neurodegeneration in TDP-43-related proteinopathies. Significance Statement: Cytoplasmic aggregates of TAR DNA Binding Protein 43 (TDP-43) are the predominant pathology in over 90% of Amyotrophic lateral sclerosis (ALS) and the majority of frontotemporal lobar degeneration (FTLD-TDP) cases. Understanding how TDP-43 pathology promotes neurodegeneration may lead to therapeutic strategies to slow disease progression in humans. Recent reports in mouse and cell culture models suggest loss-of-normal TDP-43 function may drive neuronal hyperexcitability, a key physiological hallmark of ALS and possible contributor to neurodegeneration. In this study, we identified region-specific hyperexcitability that precedes neurodegeneration in the inducible rNLS8 TDP-43 mouse model. Suppressing hyperexcitability with chemogenetics improved behavioral function but did not reduce hippocampal neuron loss. Anti-seizure medications had no beneficial effects suggesting directly targeting hyperexcitability may not be therapeutically effective.

The construction and application of a trauma limb salvage map in Shaanxi province.

Trauma is an important cause of death in young- and middle-aged people. Trauma is comprehensive and includes many surgical specialties, and the surgical techniques of these specialties have long been mature. To reduce the mortality and disability rate of trauma patients, it is necessary to improve trauma management. Trauma has attracted attention in China and trauma treatment and care developed rapidly in recent years. To decrease traumatic mortality and disability rates, our team is committed to building an efficient trauma system in Shaanxi province and has successfully developed a trauma limb salvage map to address the high rates of amputation and disability in patients with limb injuries. This article elaborates on the construction experience of a trauma limb salvage map and its application details in Shaanxi province of China.

One-Photon-Interference Quantum Secure Direct Communication.

Quantum secure direct communication (QSDC) is a quantum communication paradigm that transmits confidential messages directly using quantum states. Measurement-device-independent (MDI) QSDC protocols can eliminate the security loopholes associated with measurement devices. To enhance the practicality and performance of MDI-QSDC protocols, we propose a one-photon-interference MDI QSDC (OPI-QSDC) protocol which transcends the need for quantum memory, ideal single-photon sources, or entangled light sources. The security of our OPI-QSDC protocol has also been analyzed using quantum wiretap channel theory. Furthermore, our protocol could double the distance of usual prepare-and-measure protocols, since quantum states sending from adjacent nodes are connected with single-photon interference, which demonstrates its potential to extend the communication distance for point-to-point QSDC.

[Transurethral resection of the prostate versus transurethral columnar balloon dilatation of the prostate in the treatment of benign prostatic hyperplasia].

OBJECTIVE: To compare the effects of transurethral resection of the prostate (TURP) and transurethral columnar balloon dilatation of the prostate (TUCBDP) in the treatment of BPH. METHODS: This study included 218 BPH patients treated in Qinhuangdao Workers' Hospital from July 2021 to November 2022, 109 by TURP and the other 109 by TUCBDP. We followed up the patients for 12 months, observed their postoperative recovery, complications, serum pain, inflammatory index, cytokine level, urodynamic index, symptom improvement and quality of life (QOL) and compared the data obtained between the two groups of patients. RESULTS: At 12 months after surgery, the total effectiveness rate was significantly higher in the TUCBDP than in the TURP group (93.58% vs 84.40%, P< 0.05), and the postoperative recovery was better in the former than in the latter (P< 0.05). Compared with the baseline, the levels of serum prostaglandin E2 (PGE2), substance P, tumor necrosis factor-alpha (TNF-α) and high sensitive C-reactive protein (hs-CRP) were remarkably increased in both of the groups on the first day after surgery (P< 0.05), more significantly in the TURP than in the TUCBDP group (P< 0.05), while the levels of serum PSA and E2 decreased and the T level elevated in all the patients at 3 months postoperatively (P< 0.05), more significantly in the TUCBDP than in the TURP group (P< 0.05). Before and at 3 and 12 months after operation, the postvoid residual urine volume (PVR) and NIH-CPSI, IPSS and QOL scores showed a decreasing trend, while the maximum urinary flow rate (Qmax), maximum cystometric capacity (MCC) and maximum urethral closure pressure (MUCP) exhibited an increasing trend in both of the two groups, even more significantly in the TUCBDP than in the TURP group (P< 0.05). CONCLUSION: TUCBDP is advantageous over TURP in promoting postoperative recovery, improving QOL, reducing postoperative pain, inflammation and complications, regulating the levels of serum cytokines, and improving urodynamics and clinical symptoms in BPH patients. However, with the extension of postoperative time, the two strategies are basically comparable in improving the urodynamics, symptoms and QOL of the patients.

Early inhibition of the ATM/p53 pathway reduces the susceptibility to atrial fibrillation and atrial remodeling following acute myocardial infarction.

Atrial fibrillation (AF) emerges as a critical complication following acute myocardial infarction (AMI) and is associated with a significant increased risk of heart failure, stroke and mortality. Ataxia telangiectasia mutated (ATM), a key player in DNA damage repair (DDR), has been implicated in multiple cardiovascular conditions, however, its involvement in the development of AF following AMI remains unexplored. This study seeks to clarify the contribution of the ATM/p53 pathway in the onset of AF post-AMI and to investigate the underlying mechanisms. The rat model of AMI was established by ligating left anterior descending coronary artery in the presence or absence of Ku55933 (an ATM kinase inhibitor, 5 mg/kg/d) treatment. Rats receiving Ku55933 were further divided into the early administration group (administered on days 1, 2, 4, and 7 post-AMI) and the late administration group (administered on days 8, 9, 11 and 14 post-AMI). RNA-sequencing was performed 14 days post-operation. In vitro, H2O2-challenged HL-1 atrial muscle cells were utilized to evaluate the potential effects of different ATM inhibition schemes, including earlier, middle, and late periods of intervention. Fourteen days post-AMI injury, the animals exhibited significantly increased AF inducibility, exacerbated atrial electrical/structural remodeling, reduced ventricular function and exacerbated atrial DNA damage, as evidenced by enhanced ATM/p53 signaling as well as γH2AX level. These effects were partially consistent with the enrichment results of bioinformatics analysis. Notably, the deleterious effects were ameliorated by early, but not late, administration of Ku55933. Mechanistically, inhibition of ATM signaling successfully suppressed atrial NLRP3 inflammasome-mediated pyroptotic pathway. Additionally, the results were validated in the in vitro experiments demonstrating that early inhibition of Ku55933 not only attenuated cellular ATM/p53 signaling, but also mitigated inflammatory response by reducing NLRP3 activation. Collectively, hyperactivation of ATM/p53 contributed to the pathogenesis of AF following AMI. Early intervention with ATM inhibitors substantially mitigated AF susceptibility and atrial electrical/structural remodeling, highlighting a novel therapeutic avenue against cardiac arrhythmia following AMI.

Association between dietary glycine intake and the prevalence of hypertension, hyperlipidemia, overweight or obesity in rural northern China: a cross-sectional study.

Objective: The objective of this research is to investigate the relationship between dietary glycine consumption and the prevalence of hypertension, hyperlipidemia, and overweight or obesity in economically disadvantaged areas of northern China using a cross-sectional study design. Methods: A cross-sectional study involving 774 participants utilized a web-based dietary questionnaire (IDQC) and underwent physical measurements. Data analysis was conducted using IBM SPSS Statistics software (Version 21). Participants were stratified into four groups based on quartiles of their dietary glycine intake: Q1 (<1.32), Q2 (1.32-1.82), Q3 (1.82-2.26), and Q4 (>2.26). Continuous variables were reported as mean ± standard deviation and compared using ANOVA or the Kruskal-Wallis test, while categorical variables were presented as frequencies (%) and compared using the chi-square test. Finally, multivariable logistic regression with p-value of less than 0.05 was considered statistically significant. Results: Significant differences in dietary glycine intake were observed between the highest quartile group (Q4) and the lowest quartile group (Q1), with corresponding dominance ratios of 0.590 (95% CI, 0.360-0.966), 0.547 (95% CI, 0.327-0.913), and 0.547 (95% CI, 0.353-0.850) for the risk of hypertension, hyperlipidemia, and overweight/obesity, respectively. Furthermore, no significant correlation was found between dietary glycine intake and hypertension or hyperlipidemia within each sex and age subgroup. Conclusion: There exists a potential correlation between increased dietary glycine intake and reduced prevalence of hypertension, hyperlipidemia, and overweight/obesity. However, additional research is necessary to validate this finding through larger-scale studies conducted at a population level.

Refining metallic nano-copper by electron-rich black carbon for superior Fenton-like catalysis in water purification: The capacitive regulation of corrosive electron transfer.

Transition metals are promising catalysts for environmental remediation. However, their low reactivity, poor stability and weak reusability largely limit practical applications. Herein, we report that the electron-rich dissolved black carbon (DBC) incorporated into the nanoscale zero-valent copper (nZVCu) can boost intrinsic reactivity, structural stability and cyclic reusability for superior peroxymonosulfate (PMS) activation and pollutant degradation. A series of refractory pollutants can be effectively removed on the DBC/nZVCu, in comparison with the nZVCu reference. Hydroxyl radical (‧OH) is identified as the dominant reactive oxygen species by electron spin resonance (ESR) and chemical quenching tests, mediated by the metastable Cu(III) as the key reactive intermediate. The electron-rich DBC protects nanoscale Cu from oxidative corrosion to slow down the surface formation of inert CuO layer, rendered by the thermodynamically and dynamically capacitive regulation of corrosive electron transfer from metallic core. By this refining way, the conducive DBC improves the neighboring utilization of reactive electron during metal corrosion, oxidant activation, radical generation and pollutant degradation in Fenton-like catalysis. Our findings suggest that the ubiquitous DBC can be an efficient chelating agent to refine transition metals by serving as the surface deactivator and electron mediator, and take new insights into their environmental and agricultural geochemistry.

Fabrication of Microgel-Modified Hydrogel Flexible Strain Sensors Using Electrohydrodynamic Direct Printing Method.

Hydrogel flexible strain sensors, renowned for their high stretchability, flexibility, and wearable comfort, have been employed in various applications in the field of human motion monitoring. However, the predominant method for fabricating hydrogels is the template method, which is particularly inefficient and costly for hydrogels with complex structural requirements, thereby limiting the development of flexible hydrogel electronic devices. Herein, we propose a novel method that involves using microgels to modify a hydrogel solution, printing the hydrogel ink using an electrohydrodynamic printing device, and subsequently forming the hydrogel under UV illumination. The resulting hydrogel exhibited a high tensile ratio (639.73%), high tensile strength (0.4243 MPa), and an ionic conductivity of 0.2256 S/m, along with excellent electrochemical properties. Moreover, its high linearity and sensitivity enabled the monitoring of a wide range of subtle changes in human movement. This novel approach offers a promising pathway for the development of high-performance, complexly structured hydrogel flexible sensors.

Celastrol inhibits mouse B16-F10 melanoma cell survival by regulating the PI3K/AKT/mTOR signaling pathway and repressing HIF-1α expression.

OBJECTIVE: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway. METHODS: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway. RESULTS: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator. CONCLUSION: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA.

A microporous bismuth-based MOF for efficient separation of acetylene from carbon dioxide.

The separation of acetylene from carbon dioxide is challenging due to their almost identical molecular sizes and volatilities. Metal-organic frameworks (MOFs) in general are strong candidates for the separation of gas mixtures owing to the presence of functional pore surfaces that can selectively capture specific target molecules. Herein, we report a stable and easily synthesized bismuth-based MOF, Bi-BTC, which can achieve the separation of acetylene and carbon dioxide. We performed a detailed analysis of the sorption properties of the Bi-MOF. Bi-BTC shows good adsorption capacities for C2H2 with a capacity of 53.8 cm3 g-1 at 298 K and 1.0 bar, and C2H2/CO2 selectivity of 5.14/7.69 at 298 K and 1.0/0.1 bar. IAST selectivity calculations indicate that Bi-BTC possesses good separation capacity, and dynamic breakthrough experiments were performed to prove the separation of C2H2 and CO2. Bi-MOFs as a group of relatively less studied types of MOFs have interesting adsorption characteristics, and this study on Bi-based MOF will enrich three-dimensional Bi-MOF adsorbents for gas adsorption and separation applications.

Flexible tactile sensors with interlocking serrated structures based on stretchable multiwalled carbon nanotube/silver nanowire/silicone rubber composites.

Flexible tactile sensors have attracted significant interest because of their application scope in the fields of biomedicine, motion detection, and human-computer interaction. However, the development of tactile sensors with high sensitivity and flexibility remains a critical challenge. This study develops a patterned, stretchable, and fully elastomeric multiwalled carbon nanotube (MWCNT)/silver nanowire (Ag NW)/silicone rubber (SR) composite. The addition of Ag NWs to MWCNTs enhances the transmission path of the conductive network, yielding a CNT/Ag NW/SR composite with a sensitivity coefficient of 40. This characteristic renders it suitable for use as a piezoresistive sensing material. The interlocking sawtooth structure can convert the mechanical stimuli of the sensor to the tensile strain of the composite, thereby enhancing its sensitivity and flexibility. Experimental results indicate that the developed tactile sensor exhibited a sensitivity of 2.82 N-1 at 0-0.5 N and 1.51 N-1 at 0.5-2 N. These haptic sensors also demonstrate good dynamic response, repeatability, and long life. Furthermore, experimental results show that these haptic sensors exhibit high reproducibility, fast dynamic response, and good mechanical and electrical stability. Because of these exceptional properties, the as-prepared sensor can be applied in the development of smart robots, prosthetics, and wearable devices.

Reversible synaptic adaptations in a subpopulation of murine hippocampal neurons following early-life seizures.

Early-life seizures (ELSs) can cause permanent cognitive deficits and network hyperexcitability, but it is unclear whether ELSs induce persistent changes in specific neuronal populations and whether these changes can be targeted to mitigate network dysfunction. We used the targeted recombination of activated populations (TRAP) approach to genetically label neurons activated by kainate-induced ELSs in immature mice. The ELS-TRAPed neurons were mainly found in hippocampal CA1, remained uniquely susceptible to reactivation by later-life seizures, and displayed sustained enhancement in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated (AMPAR-mediated) excitatory synaptic transmission and inward rectification. ELS-TRAPed neurons, but not non-TRAPed surrounding neurons, exhibited enduring decreases in Gria2 mRNA, responsible for encoding the GluA2 subunit of the AMPARs. This was paralleled by decreased synaptic GluA2 protein expression and heightened phosphorylated GluA2 at Ser880 in dendrites, indicative of GluA2 internalization. Consistent with increased GluA2-lacking AMPARs, ELS-TRAPed neurons showed premature silent synapse depletion, impaired long-term potentiation, and impaired long-term depression. In vivo postseizure treatment with IEM-1460, an inhibitor of GluA2-lacking AMPARs, markedly mitigated ELS-induced changes in TRAPed neurons. These findings show that enduring modifications of AMPARs occur in a subpopulation of ELS-activated neurons, contributing to synaptic dysplasticity and network hyperexcitability, but are reversible with early IEM-1460 intervention.

[Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain].

OBJECTIVE: To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model. METHODS: Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted. RESULTS: In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05). CONCLUSION: Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Conductivity enhancement of Ag nanowire ink by decoratingin situformed Ag particles under low-temperature sintering.

Silver nanowires (AgNWs) have attractive applications in the fabrication of flexible electronics because of their adequate electrical conductivity, mechanical properties, and oxidation resistance. However, the film produced by AgNW ink needs to be sintered at temperatures above 200 °C to obtain high electrical conductivity, which is incompatible with commonly used flexible substrates such as paper or polymer materials. In this study, the AgNW network was decorated byin situreduced Ag particles (AgPs) to improve the structural integrity and conductivity of the film. After sintering at 80 °C, the pores and voids within the AgNW network were filled with Ag particles smaller than 200 nm, and the porosity of the film was markedly reduced. The lowest resistivity value was 3.9 × 10-5Ω cm after sintering at 100 °C, only 10.8% and 8.5% of the resistivity values of the films produced from AgNW and ion inks, respectively. During sintering, Ag nucleated on the surface of AgNWs, and its growth and agglomeration resulted in interconnections between the AgNWs and Ag particles. Thereafter, the bridging and filling effect of the Ag particles facilitated the formation of a compact and firm network, improving the film conductivity. The line film printed from the composite ink with 10 layers exhibited a low resistivity of 7.3 × 10-7Ω·m. Even after 5000 bending cycles, the resistivity of the line only increased by 4.47 × 10-6Ω·cm from the initial value. The composite ink reported in this study is a promising candidate for the low-cost printing of ultralow-power-consumption wearable electronic devices.

Constructing 3D flower-like S-scheme N-Bi2O2CO3/g-C3N4 heterojunction with enhanced photocatalytic performance.

Mineral processing wastewater contains a lot of organic matter and heavy metal ions, and poor self-degradation ability makes it a key treatment object in environmental treatment. Photocatalysis is a promising technology to efficiently mineralize refractory contaminants from wastewater. In this work, 3D flower-like S-scheme N-Bi2O2CO3/g-C3N4 heterostructures were successfully constructed by hydrothermal method with the auxiliary of ionic liquids. The photocatalytic experiments show that the catalytic activity of heterojunction photocatalysts was significantly higher than that of bare g-C3N4 and N-Bi2O2CO3 for the degradation of two pollutants. NBOC/CN-2 shows the highest photocatalytic performance, and the degradation efficiency of sodium isobutyl xanthate (SIBX) on NBOC/CN-2 is 1.85 and 3 times that of bare g-C3N4 and Bi2O2CO3, respectively. The degradation efficiency of m-Cresol on NBOC/CN-2 is 8.34 and 6.93 times that of bare g-C3N4 and N-Bi2O2CO3, respectively. This significantly enhanced photocatalytic activity is attributed to the formation of flower-like heterojunctions, which can greatly increase the specific surface area and facilitate the separation and migration of photogenerated carriers. Total organic carbon (TOC) experiment proves that the two pollutants are effectively mineralized under the action of the prepared photocatalyst. The degradation path of m-Cresol degradation products was inferred based on the ion fragments. The capture experiment and Nitro-blue tetrazolium (NBT)-•O2- measurement show that superoxide radical plays a major role in photocatalytic degradation. The outstanding stability of the prepared flower-like heterojunction samples was examined by cyclic experiments. The S-scheme charge transfer mechanism has been proposed to explain the boosted activity of the flower-like heterojunction photocatalyst. This work provides a new idea for the design of efficient and stable g-C3N4-based photocatalyst for the photocatalytic degradation of refractory wastewater.

Complexity of spin configuration dynamics due to unitary evolution and periodic projective measurements.

We study the Hamiltonian dynamics of a many-body quantum system subjected to periodic projective measurements, which leads to probabilistic cellular automata dynamics. Given a sequence of measured values, we characterize their dynamics by performing a principal component analysis (PCA). The number of principal components required for an almost complete description of the system, which is a measure of complexity we refer to as PCA complexity, is studied as a function of the Hamiltonian parameters and measurement intervals. We consider different Hamiltonians that describe interacting, noninteracting, integrable, and nonintegrable systems, including random local Hamiltonians and translational invariant random local Hamiltonians. In all these scenarios, we find that the PCA complexity grows rapidly in time before approaching a plateau. The dynamics of the PCA complexity can vary quantitatively and qualitatively as a function of the Hamiltonian parameters and measurement protocol. Importantly, the dynamics of PCA complexity present behavior that is considerably less sensitive to the specific system parameters for models which lack simple local dynamics, as is often the case in nonintegrable models. In particular, we point out a figure of merit that considers the local dynamics and the measurement direction to predict the sensitivity of the PCA complexity dynamics to the system parameters.

Integrated UHPLC-QE/MS, transcriptomics and network pharmacology reveal the mechanisms via which Liang-Yan-Yi-Zhen-San promotes the browning of white adipose tissue.

We have previously shown that Liang-Yan-Yi-Zhen-San (LYYZS), an ancient Chinese herbal formula, can promote the browning of white adipose tissue. In this study, we sought to determine which active ingredients of LYYZS mediated its effects on the browning of white adipose tissue. Employing ultra-high performance liquid chromatography-Q-Exactive HF mass spectrometry, a total of 52 LYYZS ingredients were identified. On this basis, 1,560 ingredient-related targets of LYYZS were screened using the HERB databases. Meanwhile, RNA sequencing analysis of the inguinal white adipose tissue of mice produced a total of 3148 genes that were significantly differentially expressed following LYYZS treatment and differentially expressed genes regarded as browning-related targets. Through the network pharmacological analysis, a total of 136 intersection targets were obtained and an ingredient-target-pathway network was established. According to network pharmacology analysis, 10 ingredients containing trans-cinnamaldehyde, genistein, daidzein, calycosin, arginine, coumarin, oleic acid, isoleucine, palmitic acid and tyrosine were regarded as active ingredients of browning of white adipose tissue. Integrated evaluation using chemical analysis, transcriptomics and network pharmacology provides an efficient strategy for discovering the active ingredients involved in how LYYZS promotes the browning of white adipose tissue.

Safety, immunogenicity and immune-persistence of heterologous prime-boost immunization with BBIBP-CorV and ZF2001 against SARS-CoV-2 in healthy adults aged 18 years or older.

BACKGROUND: Because SARS-CoV-2 mutations and immunity wane over time, a third dose of heterologous COVID-19 vaccine is proposed for individuals primed with inactivated COVID-19 vaccine. RESEARCH DESIGN AND METHODS: We conducted a single-center, open-label trial to assess the safety, immunogenicity, and immune-persistence of a heterologous BBIBP-CorV/ZF2001 prime-boost vaccination in Chinese adults. 480 participants who had been primed with two doses of BBIBP-CorV, received a third dose of ZF2001 after an interval of 3-4, 5-6, or 7-9 months. RESULTS: The overall incidence of adverse reactions within 30 days after vaccination was 5.83%. No serious adverse reactions were reported. The respective geometric mean titers (GMTs) of neutralizing antibodies for 3-4, 5-6, and 7-9 months groups at baseline were 2.06, 2.02, and 2.10; which increased to 55.42, 63.45, and 62.06 on day 14; then decreased to 17.53, 23.79, and 26.73 on day 30; before finally waning to 8.29, 9.24, and 9.51 on day 180. After the booster, the three groups showed no significant differences in GMTs. GMTs were lower in older participants than younger participants. CONCLUSIONS: A heterologous BBIBP-CorV/ZF2001 prime-boost vaccination was safe and immunogenic. Prime-boost intervals did not affect the immune response. The immune response was weaker in older adults than younger adults. CLINICAL TRIAL IDENTIFIER: NCT05205083.

Investigation of the Fabrication of Diamond/SiC Composites Using α-Si3N4/Si Infiltration.

Diamond/SiC (Dia/SiC) composites possess excellent properties, such as high thermal conductivity and low thermal expansion coefficient. In addition, they are suitable as electronic packaging materials. This study mainly optimized the diamond particle size packing and liquid-phase silicon infiltration processes and investigated a method to prevent the adhesion of the product to molten silicon. Based on the Dinger-Funk particle stacking theory, a multiscale diamond ratio optimization model was established, and the volume ratio of diamond particles with sizes of D20, D50, and D90 was optimized as 1:3:6. The method of pressureless silicon infiltration and the formulas of the composites were investigated. The influences of bedding powder on phase composition and microstructure were studied using X-ray diffraction and scanning electron microscopy, and the optimal parameters were obtained. The porosity of the preform was controlled by regulating the feeding amount through constant volume molding. Dia/SiC-8 exhibited the highest density of 2.73 g/cm3 and the lowest porosity of 0.6%. To avoid adhesion between the sample and buried powder with the bedding silicon powder, a mixed powder of α-Si3N4 and silicon was used as the buried powder and the related mechanisms of action were discussed.