Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis.

Introduction: We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM). Methods: Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493. Results: According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events. Discussion: In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.

Demonstration of 10 nm Ferroelectric Al0.7Sc0.3N-Based Capacitors for Enabling Selector-Free Memory Array.

In this work, 10 nm scandium-doped aluminum nitride (AlScN) capacitors are demonstrated for the construction of the selector-free memory array application. The 10 nm Al0.7Sc0.3N film deposited on an 8-inch silicon wafer with sputtering technology exhibits a large remnant polarization exceeding 100 µC/cm2 and a tight distribution of the coercive field, which is characterized by the positive-up-negative-down (PUND) method. As a result, the devices with lateral dimension of only 1.5 µm show a large memory window of over 250% and a low power consumption of ~40 pJ while maintaining a low disturbance rate of <2%. Additionally, the devices demonstrate stable multistate memory characteristics with a dedicated operation scheme. The back-end-of-line (BEOL)-compatible fabrication process, along with all these device performances, shows the potential of AlScN-based capacitors for the implementation of the high-density selector-free memory array.

Paxlovid use is associated with lower risk of cardiovascular diseases in COVID-19 patients with autoimmune rheumatic diseases: a retrospective cohort study.

BACKGROUND: Paxlovid has been shown to be effective in reducing mortality and hospitalization rates in patients with coronavirus disease 2019 (COVID-19). It is not known whether Paxlovid can reduce the risk of cardiovascular diseases (CVD) in COVID-19-surviving patients with autoimmune rheumatic diseases (AIRDs). METHODS: TriNetX data from the US Collaborative Network were used in this study. A total of 5,671,395 patients with AIRDs were enrolled between January 1, 2010, and December 31, 2021. People diagnosed with COVID-19 were included in the cohort (n = 238,142) from January 1, 2022, to December 31, 2022. The Study population was divided into two groups based on Paxlovid use. Propensity score matching was used to generate groups with matched baseline characteristics. The hazard ratios (HRs) and 95% confidence intervals of cardiovascular outcomes, admission rate, mortality rate, and intensive care unit (ICU) admission rate were calculated between Paxlovid and non-Paxlovid groups. Subgroup analyses on sex, age, race, autoimmune diseases group, and sensitivity analyses for Paxlovid use within the first day or within 2-5 days of COVID-19 diagnosis were performed. RESULTS: Paxlovid use was associated with lower risks of cerebrovascular complications (HR = 0.65 [0.47-0.88]), arrhythmia outcomes (HR = 0.81 [0.68-0.94]), ischemic heart disease, other cardiac disorders (HR = 0.51 [0.35-0.74]) naming heart failure (HR = 0.41 [0.26-0.63]) and deep vein thrombosis (HR = 0.46 [0.24-0.87]) belonging to thrombotic disorders in AIRD patients with COVID-19. Compared with the Non-Paxlovid group, risks of major adverse cardiac events (HR = 0.56 [0.44-0.70]) and any cardiovascular outcome mentioned above (HR = 0.76 [0.66-0.86]) were lower in the Paxlovid group. Moreover, the mortality (HR = 0.21 [0.11-0.40]), admission (HR = 0.68 [0.60-0.76]), and ICU admission rates (HR = 0.52 [0.33-0.80]) were significantly lower in the Paxlovid group than in the non-Paxlovid group. Paxlovid appears to be more effective in male, older, and Black patients with AIRD. The risks of cardiovascular outcomes and severe conditions were reduced significantly with Paxlovid prescribed within the first day of COVID-19 diagnosis. CONCLUSIONS: Paxlovid use is associated with a lower risk of CVDs and severe conditions in COVID-19-surviving patients with AIRD.

Enhancing the tumor penetration of multiarm polymers by collagenase modification.

Tumor penetration is a critical determinant of the therapy efficacy of nanomedicines. However, the dense extracellular matrix (ECM) in tumors significantly hampers the deep penetration of nanomedicines, resulting in large drug-untouchable areas and unsatisfactory therapy efficacy. Herein, we synthesized a third-generation PAMAM-cored multiarm copolymer and modified the polymer with collagenase to enhance its tumor penetration. Each arm of the copolymer was a diblock copolymer of poly(glutamic acid)-b-poly(carboxybetaine), in which the polyglutamic acid block with abundant side groups was used to link the anticancer agent doxorubicin through the pH-sensitive acylhydrazone linkage, and the zwitterionic poly(carboxybetaine) block provided desired water solubility and anti-biofouling capability. The collagenase was conjugated to the ends of the arms via the thiol-maleimide reaction. We demonstrated that the polymer-bound collagenase could effectively catalyze the degradation of the collagen in the tumor ECM, and consequently augmented the tumor penetration and antitumor efficacy of the drug-loaded polymers.

A preliminary study on analysis of lower limb energy during walking in the patients with knee replacement.

Background: Knee replacement surgeries are used to reduce pain and enhance functionality for individuals with knee arthritis. It is predicted that the annual volume of total knee replacement surgeries conducted in the US will surge by a substantial 673% by 2030. Though a lot of studies have done gait analysis on patients with knee replacement, little research is on energy changes in the lower limbs during gait. This study aimed to investigate the mechanical energy changes in the lower limbs for patients with total knee arthroplasty (TKA) and unicondylar knee arthroplasty (UKA), and ultimately to provide a specific tool to analyze limb energy during gait in clinical practice. Methods: 10 TKA and 8 UKA patients were recruited for gait analysis. The control group consisted of 11 individuals without knee replacement surgery. Vicon motion capture system and Plug-in-Gait model were used to collect gait data to obtain marker coordinates and gait parameters. The kinetic energy, potential energy, and rotational energy for each segment in the lower limbs were calculated. The energies in the centre of pelvis were considered as the approximate to the centre of mass. The energy recovery coefficients were analysed for each segment during gait. SPSS was used to identify the differences between different groups. Results: The results showed that during walking, the upper leg had the highest recovery coefficient, approximately 40%, followed by the foot at 10%, and the lowest recovery coefficient was observed in the lower leg, approximately 1-3%. However, the energy recovery coefficients at the centre of pelvis were significantly higher in the control group than the TKA and UKA groups by roughly 12%-15%. Conclusions: The energy difference between the operative and non-operative sides is not significant regardless of the type of surgery. The TKA and UKA groups were more active in potential energy than control group. The upper leg has the highest recovery efficiency of kinetic and potential energy exchanges when walking. The control group used the energy for whole body is better than the patient groups. This study provides a new and useful way to analyze mechanical energy in the lower limbs during gait and could be applied in clinical practice.

Model construction and application for predicting pre-eclampsia by Sonoclot coagulation analyzer.

Maternal age has significantly increased among Chinese women, thereby posing risk of pregnancy-related complications. Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, and coagulation analysis in conjunction with clinical signs and symptoms are generally used for its diagnosis with limited efficacy. Sonoclot coagulation analyzer is effective in assessing coagulation function used during cerebral surgery and cardiovascular surgery. However, its use has not been explored in preeclampsia. Here, we investigated the potential use of Sonoclot in diagnosing preeclampsia in obstetrics cases. Subjects meeting the screening criteria were divided either into a test group or a control group, according to whether they were preeclamptic or not. We recorded the Sonoclot-derived coagulation and the routine coagulation parameters including platelet function (PF), activated clotting time (ACT) and clot rate (CR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and platelet count. Regression analysis was done on the relevant parameters to assess the feasibility of Sonoclot analyzer in preeclampsia diagnosis. In parallel, changes in preeclampsia lncRNAs was also evaluated. Significant differences were recorded in PT and ACT between the two groups. In the monovariant logistic regression, PT and ACT appeared to be reliable predictor variables. In the multinomial logistic regression, a total of five regression steps were performed with decreasing AIC values. The K-fold cross validation resulted in an accuracy rate (ACC) of 77.5%, a false positive rate of 16.4%, and a false negative rate of 33.2%. lncRNAs ANRIL and HOXD-AS1 were found deregulated. Our findings indicate that Sonoclot may be useful for diagnosis of preeclampsia in obstetrics.

Nrf2 activation by neferine mitigates microglial neuroinflammation after subarachnoid hemorrhage through inhibiting TAK1-NF-κB signaling.

Oxidative stress and neuroinflammation are two major causes leading to early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor E2-related factor 2 (Nrf2) is a critical transcription factor that contributes to antioxidant responses. Additionally, Nrf2 could inhibit transforming growth factor beta-activated kinase 1 (TAK1), which plays a vital role in microglial activation-mediated neuroinflammation. Neferine (NE) exhibits considerable protective effects in diverse disease models. However, the detailed effect and mechanism of NE on SAH remain unknown. Our data showed that NE treatment significantly reduced behavior and cognitive impairment, and brain edema in the early period after SAH. In addition, NE mitigated SAH-induced oxidative damage, neuroinflammation, and neural death. Moreover, NE inhibited M1 microglial polarization and enhanced M2 phenotype microglia both in vivo and in vitro. Further investigations revealed that NE enhanced the Nrf2-antioxidant response element (ARE) signaling pathway and suppressed TAK1-NF-κB signaling. In contrast, depletion of Nrf2 by ML385 suppressed Nrf2-ARE signaling, induced TAK1-NF-κB activation, and further promoted M1 microglial polarization. Additionally, ML385 abated the neuroprotective effects of NE against SAH. Notably, LPS also aggravated TAK1-NF-κB activation and reversed the beneficial effects of NE after SAH. In summary, NE provides protection after SAH by inhibiting oxidative stress and modulating microglial polarization through Nrf2 activation and TAK1-NF-κB suppression.

Epidemiology of gout - Global burden of disease research from 1990 to 2019 and future trend predictions.

Background: Understanding the global burden of gout in the past and future can provide important references for optimizing prevention and control strategies in healthcare systems. Objectives: This study aimed to report variations in the global disease burden and risk factors of gout in 204 countries and territories from 1990 to 2019. Design: We conducted a retrospective analysis of gout based on the latest Global Burden of Disease (GBD) 2019 database. Methods: We collected data on the prevalence, incidence, and disability-adjusted life years (DALYs) of gout from 1990 to 2019. The data were then stratified by age, sex, and economic development level. Decomposition analysis, frontier analysis, and prediction models were used to analyze the changes and influencing factors influencing each indicator. Results: Globally, there were 53,871,846.4 [95% uncertainty interval (UI): 43,383,204.6-66,342,327.3] prevalent cases, 92,228,86.8 (95% UI: 7419,132.1-11,521,165) incident cases, and 1673,973.4 (95% UI: 1,068,061.1-2,393,469.2) cases of DALYs of gout in 2019, more than double those in 1990. Moreover, the pace of increase in the age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), and age-standardized DALY rate (ASDR) accelerated during 1990-2019, with estimated annual percentage changes (EAPC) of 0.94 [95% confidence interval (CI): 0.85-1.03], 0.77 (95% CI: 0.69-0.84), and 0.93 (95% CI: 0.84-1.02), respectively, especially among men. The disease burden of gout has increased in all the other 20 GBD regions in the past 30 years, except Western Sub-Saharan Africa. The highest risk of high body mass index (BMI) and kidney dysfunction was in high-income countries such as North America and East Asia. The global prevalence rate, incidence rate, and DALYs rate of gout in 2030 will reach 599.86, 102.96 per 100,000 population, and 20.26 per 100,000 population, respectively, roughly the same as in 2019. Conclusion: With the development of society, the disease burden of gout will become increasingly severe. It is very important to study the accurate epidemiological data on gout for clinical diagnosis and treatment and health policy.

Neutralization of SARS-CoV-2 BA.2.86 and JN.1 by CF501 adjuvant-enhanced immune responses targeting the conserved epitopes in ancestral RBD.

The emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2.86 and JN.1 raise concerns regarding their potential to evade immune surveillance and spread globally. Here, we test sera from rhesus macaques immunized with 3 doses of wild-type SARS-CoV-2 receptor-binding domain (RBD)-Fc adjuvanted with the STING agonist CF501. We find that the sera can potently neutralize pseudotyped XBB.1.5, XBB.1.16, CH.1.1, EG.5, BA.2.86, and JN.1, with 50% neutralization titers ranging from 3,494 to 7,424. We also demonstrate that CF501, but not Alum, can enhance immunogenicity of the RBD from wild-type SARS-CoV-2 to improve induction of broadly neutralizing antibodies (bnAbs) with binding specificity and activity similar to those of SA55, BN03, and S309, thus exhibiting extraordinary broad-spectrum neutralizing activity. Overall, the RBD from wild-type SARS-CoV-2 also contains conservative epitopes. The RBD-Fc adjuvanted by CF501 can elicit potent bnAbs against JN.1, BA.2.86, and other XBB subvariants. This strategy can be adopted to develop broad-spectrum vaccines to combat future emerging and reemerging viral infectious diseases.

A coumarin-furoxan hybrid as novel nitric oxide donor induced cell apoptosis and ferroptosis in NSCLC by promoting S-nitrosylation of STAT3 and negative regulation of JAK2-STAT3 pathway.

Non-small cell lung cancer (NSCLC) still lacks effective treatment because of its extensive mutation diversity and frequent drug resistance. Therefore, it is urgent to develop new therapeutic strategies for NSCLC. In this study, we evaluated the inhibitory effect of a new coumarin-furoxan hybrid compound 9, a nitric oxide (NO) donor drug, on NSCLC proliferation and its mechanism. Our results show that compound 9 can inhibit the growth of four NSCLC cell lines and H1975 xenograft model in a dose-dependent manner. Compound 9 effectively releases high concentrations of NO within the mitochondria, leading to cellular oxidative stress, mitochondrial dysfunction, and apoptosis. Moreover, compound 9 inhibits JAK2/STAT3 protein phosphorylation and induces S-nitrosylation modification of STAT3, ultimately resulting in endogenous apoptosis in NSCLC. Additionally, compound 9 significantly induces NSCLC ferroptosis by depleting intracellular GSH, elevating MDA levels, inhibiting SLC7A11/GSH protein expression, and negatively regulating the JAK2/STAT3 pathway. In summary, this study elucidates the inhibitory effects of compound 9 on NSCLC proliferation and provides insights into the underlying mechanisms, offering new possibilities for NSCLC treatment strategies.

Spacecraft Attitude Measurement and Control Using VSMSCSG and Fractional-Order Zeroing Neural Network Adaptive Steering Law.

In order to improve the accuracy and convergence speed of the steering law under the conditions of high dynamics, high bandwidth, and a small deflection angle, and in an effort to improve attitude measurement and control accuracy of the spacecraft, a spacecraft attitude measurement and control method based on variable speed magnetically suspended control sensitive gyroscopes (VSMSCSGs) and the fractional-order zeroing neural network (FO-ZNN) steering law is proposed. First, a VSMSCSG configuration is designed to realize attitude measurement and control integration in which the VSMSCSGs are employed as both actuators and attitude-rate sensors. Second, a novel adaptive steering law using FO-ZNN is designed. The matrix pseudoinverses are replaced by FO-ZNN outputs, which solves the problem of accuracy degradation in the traditional pseudoinverse steering laws due to the complexity of matrix pseudoinverse operations under high dynamics conditions. In addition, the convergence and robustness of the FO-ZNN are proven. The results show that the proposed FO-ZNN converges faster than the traditional zeroing neural network under external disturbances. Finally, a new weighting function containing rotor deflection angles is added to the steering law to ensure that the saturation of the rotor deflection angles can be avoided. Semi-physical simulation results demonstrate the correctness and superiority of the proposed method.

Skin-Attached Arrayed Piezoelectric Sensors for Continuous and Safe Monitoring of Oculomotor Movements.

Abnormal oculomotor movements are known to be linked to various types of brain disorders, physical/mental shocks to the brain, and other neurological disorders, hence its monitoring can be developed into a simple but effective diagnostic tool. To overcome the limitations in the current eye-tracking system and electrooculography, a piezoelectric arrayed sensor system is developed using single-crystalline III-N thin-film transducers, which offers advantages of mechanical flexibility, biocompatibility, and high electromechanical conversion, for continuous monitoring of oculomotor movements by skin-attachable, safe, and highly sensitive sensors. The flexible piezoelectric eye movement sensor array (F-PEMSA), consisting of three transducers, is attached on the the face temple area where it can be comfortably wearable and can detect the muscles' activity associated with the eye motions. Output voltages from upper, mid, and lower sensors (transducers) on different temple areas generate discernable patterns of output voltage signals with different combinations of positive/negative signs and their relative magnitudes for the various movements of eyeballs including 8 directional (lateral, vertical, and diagonal) and two rotational movements, which enable various types of saccade and pursuit tests. The F-PEMSA can be used in clinical studies on the brain-eye relationship to evaluate the functional integrity of multiple brain systems and cognitive processes. This article is protected by copyright. All rights reserved.

The population affected by dust in China in the springtime.

Dust events in northern China, particularly in the springtime, affect millions of people in the source and downwind regions. We investigate the population affected by various dust levels in China in the springtime from 2003 to 2020 using satellite retrievals of dust optical depth (DOD). We select three DOD thresholds, namely DOD > 0.2, DOD > 0.3, and DOD > 0.4, to estimate the population affected and find that each year the population affected can differ by one order of magnitude. The population exposed to DOD > 0.2 ranged from 16 million (2019) to over 200 million (2006). The population exposed to DOD > 0.3 ranged from 10 million (2015) to 70 million (2006). The population exposed to DOD > 0.4 ranged from 4 million (2017) to 36 million (2006). In years when dust events are frequent, people in the source and downwind regions are both affected, whereas, in years when dust events are less frequent, people affected are mainly in the source regions. Furthermore, we use the relative index of inequality to assess whether dust hazards impose unequal pollution burdens on different socioeconomic groups. We find that low-income communities have been more likely affected by dust pollution since 2013.

Leakage Mechanism and Cycling Behavior of Ferroelectric Al0.7Sc0.3N.

Ferroelectric scandium-doped aluminum nitride (Al1-xScxN) is of considerable research interest because of its superior ferroelectricity. Studies indicate that Al1-xScxN may suffer from a high leakage current, which can hinder further thickness scaling and long-term reliability. In this work, we systematically investigate the origin of the leakage current in Al0.7Sc0.3N films via experiments and theoretical calculations. The results reveal that the leakage may originate from the nitrogen vacancies with positively charged states and fits well with the trap-assisted Poole-Frenkel (P-F) emission. Moreover, we examine the cycling behavior of ferroelectric Al0.7Sc0.3N-based FeRAM devices. We observe that the leakage current substantially increases when the device undergoes bipolar cycling with a pulse amplitude larger than the coercive electric field. Our analysis shows that the increased leakage current in bipolar cycling is caused by the monotonously reduced trap energy level by monitoring the direct current (DC) leakage under different temperatures and the P-F emission fitting.

Epidemiology of spinal cord injury and spinal cord injury-induced urinary tract stones in Taiwan: A 2005-2015 population-based cohort study.

CONTEXT: Patients with spinal cord injury (SCI) can develop urinary tract stones (UTSs) up to years after the injury, which is especially common in the first few months. However, relevant epidemiological studies and up-to-date epidemiological data for SCI in Taiwan are lacking. PURPOSE: To estimate SCI and SCI-induced UTS incidence and trauma severity, neurological deficits, and injury site in patients with SCI-induced UTSs in Taiwan. DESIGN: Retrospective cohort study.Patient sample: Taiwan National Health Insurance Research Database (NHIRD) data and death data from the Department of Health and Welfare Data Science Center (HWDC) collected over 2005-2015 from 13,977 patients with SCI aged >18 years. OUTCOME MEASURES: Cumulative incidence (CI), incidence density (ID), relative ratios (RRs), odds ratios (ORs), and hazard ratios (HRs) were measured. METHODS: By using Cox regression, we assessed UTS risk in patients with SCI. RESULTS: Although standardized SCI incidence demonstrated a decreasing trend annually, the average annual incidence remained at 60.4 per million. Most (65.7%) of the included patients were men. SCI incidence was 1.98 times higher in men than in women. The most common injury site was the cervical spine (63.8%); the incidence at this site was 2.83 times higher in men than in women. Most (76.1%) of the patients had traumatic SCI (TSCI), and the standardized incidence of TSCI and non-TSCI was 45.9 and 14.4 per million, respectively. 46.1% of the patients had severe SCI (RISS ≥ 16). Over the 11-year follow-up period, UTSs occurred in 10.4% of the patients, with a standardized incidence of 2.39 per 100 person-years, and UTS risk was 1.56 times higher in men than in women. Age of 45-65 years, SCIs at multiple sites, and neurological deficits (e.g. paraplegia) were noted to be UTS risk factors. Finally, UTS onset mainly occurred in the first year after SCI. CONCLUSION: The risk of UTS among patients with SCI is influenced by age, sex, injury site, and paraplegia but not by paralysis resulting from other neurological deficits. Even though SCI incidence is declining annually, severe SCI remains a significant issue. Therefore, continuing to reduce SCI incidence and strengthening urinary tract management in patients with SCI are essential for reducing UTS occurrence and their impact on health.

Bi-allelic missense variants in MEI4 cause preimplantation embryonic arrest and female infertility.

Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants-namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)-in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients.

Self-lysis microbial consortia for predictable multi-proteins assembly.

The scope of bioengineering is expanding from the design of single strain to the microbial communities, allowing for the division-of-labor in synthesizing the multi-protein systems. Predicting the composition of the final product during the biomanufacturing process, however, can be difficult. Consortia-based manufacturing has the potential to boost production efficiency, but this benefit primarily holds in the upstream. The current format of downstream process heavily relies on the centralized facility, and is not economical and flexible to address the demands in small-scale. Here, we present a concise and manageable platform to enable the multi-protein system assembly. We engineer a self-lysis microbial consortium, where each strain lyses autonomously at high densities and produces a single protein component. The product fraction can be precisely tuned by varying the inoculation ratio. Utilizing this platform, we assemble a classical 34-component PURE (protein synthesis using recombinant elements) system. We have further optimized the downstream process of the biomanufacturing by incorporating the porous structure of polymeric materials. The encapsulated autolysis consortium can produce and release the proteins while maintaining the cell factories enclosed in the materials by exporting the multi-protein system for collection. Our research provides a novel approach to the flexible and controllable production of multi-protein systems, opening up new possibilities for pathway assembly and portable biomanufacturing.

Stepwisely Assembled Multicomponent Fiber with High Water Content and Superior Mechanical Properties for Artificial Ligament.

The ligament, which connects bones at the joints, has both high water content and excellent mechanical properties in living organisms. However, it is still challenging to fabricate fibrous materials that possess high water content and ligament-like mechanical characteristics simultaneously. Herein, the design and preparation of a ligament-mimicking multicomponent fiber is reported through stepwise assembly of polysaccharide, calcium, and dopamine. In simulated body fluid, the resulting fiber has a water content of 40 wt%, while demonstrating strength of ≈120 MPa, a Young's modulus of ≈3 GPa, and a toughness of ≈25 MJ m-3 . Additionally, the multicomponent fiber exhibits excellent creep and fatigue resistance, as well as biocompatibility to support cell growth in vitro. These findings suggest that the fiber has potential for engineering high-performance artificial ligament.

Rumen-protected lysine supplementation improved amino acid balance, nitrogen utilization and altered hindgut microbiota of dairy cows.

This study was conducted to evaluate the effects of dietary crude protein (CP) and rumen-protected lysine (RPL) supplementation on lactation performance, amino acid (AA) balance, nitrogen (N) utilization and hindgut microbiota in dairy cows. Treatments were in a 2 × 2 factorial arrangement, and the main effects were CP concentration (16% vs. 18%) and RPL supplementation (with or without RPL at 40 g/cow per day). Forty cows were randomly allocated to 4 groups: low-CP diet (LP), low-CP diet plus RPL (LPL), high-CP diet (HP), high-CP diet plus RPL (HPL). The experiment was conducted for 8 weeks. Results showed that RPL increased the dry matter intake (P < 0.01), milk protein yield (P = 0.04) and energy corrected milk (P = 0.04), and tended to increase milk fat yield (P = 0.06) and fat corrected milk (P = 0.05). Cows in the HP group tended to have higher milk urea N (P = 0.07). Plasma concentrations of Arg, Ile, Lys, Met, Pro, total essential AA and total nonessential AA were increased by RPL (P < 0.05). The total essential AA, total nonessential AA and most AA (except Ile, Phe, Gly and Pro) were increased in the HP group (P < 0.05). N excretion was increased in the HP group through an increase in urea N excretion (P < 0.01) and an upward trend in plasma urea N (P = 0.07). In addition, RPL tended to increase milk protein N secretion (P = 0.08), milk N (P = 0.07) and microbial protein synthesis (P = 0.06), and decreased plasma urea N (P < 0.001). In the hindgut, the bacterial community were different between the LP and LPL groups (P < 0.01). The probiotic abundances of Christensenellaceae_R-7_group and Acinetobacter were increased by RPL (P = 0.03 and 0.03, respectively). The pathogenic abundances of Clostridium_sensu_stricto_1 (P < 0.001) and Turicibacter (P < 0.01) were decreased by RPL. In conclusion, supplementing RPL with low dietary CP could balance AA supply and increase milk protein yield, resulting in an improvement in N utilization efficiency, and altered the composition of the hindgut microbiota to favor the lactation performance of dairy cows.

Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice.

Traumatic brain injury (TBI) is caused by acquired damage that includes cerebral edema after a mechanical injury and may cause cognitive impairment. We explored the role of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2; NOX2) and aquaporin-4 (AQP4) in the process of edema and cognitive abilities after TBI in NOX2-/- and AQP4-/- mice by using the Morris water maze test (MWM), step-down test (STD), novel object recognition test (NOR) and western blotting. Knockout of NOX2 in mice decreased the AQP4 and reduce edema in the hippocampus and cortex after TBI in mice. Moreover, inhibiting AQP4 by 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) or genetic deletion of AQP4 could attenuate neurological deficits without changing reactive oxygen species (ROS) levels after TBI in mice. Taken together, we suspected that inhibiting NOX2 could improve cognitive abilities by modulating ROS levels, then affecting AQP4 levels and brain edema after in TBI mice. Our study demonstrated that NOX2 play a key role in decreasing edema in brain and improving cognitive abilities by modulating AQP4 after TBI.