Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.

DAMPs and DAMP-sensing receptors in inflammation and diseases.

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules produced in cellular damage or stress, and they can activate the innate immune system. DAMPs contain multiple types of molecules, including nucleic acids, proteins, ions, glycans, and metabolites. Although these endogenous molecules do not trigger immune response under steady-state condition, they may undergo changes in distribution, physical or chemical property, or concentration upon cellular damage or stress, and then they become DAMPs that can be sensed by innate immune receptors to induce inflammatory response. Thus, DAMPs play an important role in inflammation and inflammatory diseases. In this review, we summarize the conversion of homeostatic molecules into DAMPs; the diverse nature and classification, cellular origin, and sensing of DAMPs; and their role in inflammation and related diseases. Furthermore, we discuss the clinical strategies to treat DAMP-associated diseases via targeting DAMP-sensing receptors.

Janus Binder Chemistry for Synchronous Enhancement of Iodine Species Adsorption and Redox Kinetics toward Sustainable Aqueous Zn-I2 Batteries.

Currently, the desired research focus in energy storage technique innovation has been gradually shifted to next-generation aqueous batteries holding both high performance and sustainability. However, aqueous Zn-I2 batteries have been deemed to have great sustainable potential, owing to the merits of cost-effective and eco-friendly nature. However, their commercial application is hindered by the serious shuttle effect of polyiodides during reversible operations. In this work, a Janus functional binder based on chitosan (CTS) molecules was designed and prepared; the polar terminational groups impart excellent mechanical robustness to hybrid binders; meanwhile, it can also deliver isochronous enhancement on physical adsorption and redox kinetics toward I2 species. By feat of highly effective remission to shuttle effect, the CTS cell exhibits superb electrochemical storage capacities with long-term robustness, specifically, 144.1 mAh g-1, at a current density of 0.2 mA g-1 after 1500 cycles. Simultaneously, the undesired self-discharging issue could be also well-addressed; the Coulombic efficiency could remain at 98.8 % after resting for 24 h. More importantly, CTS molecules endow good biodegradability and reusable properties; after iodine species were reloaded, the recycled devices could also deliver specific capacities of 73.3 mAh g-1, over 1000 cycles. This Janus binder provides a potential synchronous solution to realize high comprehensive performance with high iodine utilization and further make it possible for sustainable Zn-I2 batteries.

Ultrafast, Selective, and Highly Sensitive Nonchromatographic Analysis of Fourteen Cannabinoids in Cannabis Extracts, Δ8-Tetrahydrocannabinol Synthetic Mixtures, and Edibles by Cyclic Ion Mobility Spectrometry-Mass Spectrometry.

The diversity of cannabinoid isomers and complexity of Cannabis products pose significant challenges for analytical methodologies. In this study, we developed a method to analyze 14 different cannabinoid isomers in diverse samples within milliseconds by leveraging the unique adduct-forming behavior of silver ions in advanced cyclic ion mobility spectrometry-mass spectrometry. The developed method achieved the separation of isomers from four groups of cannabinoids: Δ3-tetrahydrocannabinol (THC) (1), Δ8-THC (2), Δ9-THC (3), cannabidiol (CBD) (4), Δ8-iso-THC (5), and Δ(4)8-iso-THC (6) (all MW = 314); 9α-hydroxyhexahydrocannabinol (7), 9ß-hydroxyhexahydrocannabinol (8), and 8-hydroxy-iso-THC (9) (all MW = 332); tetrahydrocannabinolic acid (THCA) (10) and cannabidiolic acid (CBDA) (11) (both MW = 358); Δ8-tetrahydrocannabivarin (THCV) (12), Δ8-iso-THCV (13), and Δ9-THCV (14) (all MW = 286). Moreover, experimental and theoretical traveling wave collision cross section values in nitrogen (TWCCSN2) of cannabinoid-Ag(I) species were obtained for the first time with an average error between experimental and theoretical values of 2.6%. Furthermore, a workflow for the identification of cannabinoid isomers in Cannabis and Cannabis-derived samples was established based on three identification steps (m/z and isotope pattern of Ag(I) adducts, TWCCSN2, and MS/MS fragments). Afterward, calibration curves of three major cannabinoids were established with a linear range of 1-250 ng·ml-1 for Δ8-THC (2) (R2 = 0.9999), 0.1-25 ng·ml-1 for Δ9-THC (3) (R2 = 0.9987), and 0.04-10 ng·ml-1 for CBD (4) (R2 = 0.9986) as well as very low limits of detection (0.008-0.2 ng·ml-1). Finally, relative quantification of Δ8-THC (2), Δ9-THC (3), and CBD (4) in eight complex acid-treated CBD mixtures was achieved without chromatographic separation. The results showed good correspondence (R2 = 0.999) with those obtained by gas chromatography-flame ionization detection/mass spectrometry.

P-N Bonds-Mediated Atomic-Level Charge-Transfer Channel Fabricated between Violet Phosphorus and Carbon Nitride Favors Charge Separation and Water Splitting.

Heterostructures are widely employed in photocatalysis to promote charge separation and photocatalytic activity. However, their benefits are limited by the linkages and contact environment at the interface. Herein, violet phosphorus quantum dots (VPQDs) and graphitic carbon nitride (g-C3N4) are employed as model materials to form VPQDs/g-C3N4 heterostructures by a simple ultrasonic pulse excitation method. The heterostructure contains strong interfacial P-N bonds that mitigate interfacial charge-separation issues. P-P bond breakage occurs in the distinctive cage-like [P9] VPQD units during longitudinal disruption, thereby exposing numerous active P sites that bond with N atoms in g-C3N4 under ultrasonic pulse excitation. The atomic-level interfacial P-N bonds of the Z-scheme VPQDs/g-C3N4 heterostructure serve as photogenerated charge-transfer channels for improved electron-hole separation efficiency. This results in excellent photocatalytic performance with a hydrogen evolution rate of 7.70 mmol g-1 h-1 (over 9.2 and 8.5 times greater than those of pure g-C3N4 and VPQDs, respectively) and apparent quantum yield of 11.68% at 400 nm. Using atomic-level chemical bonds to promote interfacial charge separation in phosphorene heterostructures is a feasible and effective design strategy for photocatalytic water-splitting materials.

Droplet Microfluidics Powered Hydrogel Microparticles for Stem Cell-Mediated Biomedical Applications.

Stem cell-related therapeutic technologies have garnered significant attention of the research community for their multi-faceted applications. To promote the therapeutic effects of stem cells, the strategies for cell microencapsulation in hydrogel microparticles have been widely explored, as the hydrogel microparticles have the potential to facilitate oxygen diffusion and nutrient transport alongside their ability to promote crucial cell-cell and cell-matrix interactions. Despite their significant promise, there is an acute shortage of automated, standardized, and reproducible platforms to further stem cell-related research. Microfluidics offers an intriguing platform to produce stem cell-laden hydrogel microparticles (SCHMs) owing to its ability to manipulate the fluids at the micrometer scale as well as precisely control the structure and composition of microparticles. In this review, the typical biomaterials and crosslinking methods for microfluidic encapsulation of stem cells as well as the progress in droplet-based microfluidics for the fabrication of SCHMs are outlined. Moreover, the important biomedical applications of SCHMs are highlighted, including regenerative medicine, tissue engineering, scale-up production of stem cells, and microenvironmental simulation for fundamental cell studies. Overall, microfluidics holds tremendous potential for enabling the production of diverse hydrogel microparticles and is worthy for various stem cell-related biomedical applications.

Interfacial-Confined Isochronous Conversion to Biphasic Selenide Heterostructure with Enhanced Adsorption Behaviors for Robust High-Rate Na-Ion Storage.

Sodium-ion batteries (SIBs) have gradually become one of the most promising energy storage techniques in the current era of post-lithium-ion batteries. For anodes, transitional metal selenides (TMSe) based materials are welcomed choices , owing to relatively higher specific capacities and enriched redox active sites. Nevertheless, current bottlenecks are blamed for their poor intrinsic electronic conductivities, and uncontrollable volume expansion during redox reactions. Given that, an interfacial-confined isochronous conversion strategy is proposed, to prepare orthorhombic/cubic biphasic TMSe heterostructure, namely CuSe/Cu3 VSe4 , through using MXene as the precursor, followed by Cu/Se dual anchorage. As-designed biphasic TMSe heterostructure endows unique hierarchical structure, which contains adequate insertion sites and diffusion spacing for Na ions, besides, the surficial pseudocapacitive storage behaviors can be also proceeded like 2D MXene. By further investigation on electronic structure, the theoretical calculations indicate that biphasic CuSe/Cu3 VSe4 anode exhibits well-enhanced properties, with smaller bandgap and thus greatly improves intrinsic poor conductivities. In addition, the dual redox centers can enhance the electrochemical Na ions storage abilities. As a result, the as-designed biphasic TMSe anode can deliver a reversible specific capacity of 576.8 mAh g-1 at 0.1 A g-1 , favorable Na affinity, and reduced diffusion barriers. This work discloses a synchronous solution toward demerits in conductivities and lifespan, which is inspiring for TMSe-based anode development in SIBs systems.

Dynamic radiological features predict pathological response after neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant immunochemotherapy (NICT) plus esophagectomy has emerged as a promising treatment option for locally advanced esophageal squamous cell carcinoma (LA-ESCC). Pathologic complete response (pCR) is a key indicator associated with great efficacy and overall survival (OS). However, there are insufficient indicators for the reliable assessment of pCR. METHODS: 192 patients with LA-ESCC treated with NICT from December 2019 to October 2023 were recruited. According to pCR status, patients were categorized into pCR group (22.92%) and non-pCR group (77.08%). Radiological features of pretreatment and preoperative CT images were extracted. Logistic and COX regressions were trained to predict pathological response and prognosis, respectively. RESULTS: Four of the selected radiological features were combined to construct an ESCC preoperative imaging score (ECPI-Score). Logistic models revealed independent associations of ECPI-Score and vascular sign with pCR, with AUC of 0.918 in the training set and 0.862 in the validation set, respectively. After grouping by ECPI-Score, a higher proportion of pCR was observed among the high-ECPI group and negative vascular sign. Kaplan Meier analysis demonstrated that recurrence-free survival (RFS) with negative vascular sign was significantly better than those with positive (P = 0.038), but not for OS (P = 0.310). CONCLUSIONS: This study demonstrates dynamic radiological features are independent predictors of pCR for LA-ESCC treated with NICT. It will guide clinicians to make accurate treatment plans.

Decoherence-free-subspace-based deterministic conversions for entangled states with heralded robust-fidelity quantum gates.

The decoherence-free subspace (DFS) serves as a protective shield against certain types of environmental noise, allowing the system to remain coherent for extended periods of time. In this paper, we propose two protocols, i.e., one converts two-logic-qubit Knill-Laflamme-Milburn (KLM) state to two-logic-qubit Bell states, and the other converts three-logic-qubit KLM state to three-logic-qubit Greenberger-Horne-Zeilinger states, through cavity-assisted interaction in DFS. Especially, our innovative protocols achieve their objectives in a heralded way, thus enhancing experimental accessibility. Moreover, single photon detectors are incorporated into the setup, which can predict potential failures and ensure seamless interaction between the nitrogen-vacancy center and photons. Rigorous analyses and evaluations of two schemes demonstrate their abilities to achieve near-unit fidelities in principle and exceptional efficiencies. Further, our protocols offer progressive solutions to the challenges posed by decoherence, providing a pathway towards practical quantum technologies.

Qudit-based high-dimensional controlled-not gate.

High-dimensional quantum systems expand quantum channel capacity and information storage space. By implementing high-dimensional quantum logic gates, the speed of quantum computing can be practically enhanced. We propose a deterministic 4 × 4-dimensional controlled-not (CNOT) gate for a hybrid system without ancillary qudits required, where the spatial and polarization states of a single photon serve as a control qudit of four dimensions, whereas two electron-spin states in nitrogen-vacancy (NV) centers act as a four-dimensional target qudit. As the control qudits are easily operated employing simple optical elements and the target qudits are available for storage, the CNOT gate works in a deterministic way, and it can be flexibly extended to n × n-dimensional (n > 4) quantum gates for other hybrid systems or different photonic degrees of freedoms. The efficiency and fidelity of the CNOT gate are analyzed aligning with current technological capabilities, finding that they have satisfactory performances.

Ultrahigh Critical Current Density across Sliding Electrical Contacts in Structural Superlubric State.

In conventional sliding electrical contacts (SECs), large critical current density (CCD) requires a high ratio between actual and apparent contact area, while low friction and wear require the opposites. Structural superlubricity (SSL) has the characteristics of zero wear, near zero friction, and all-atoms in real contact between the contacting surfaces. Here, we show a measured current density up to 17.5 GA/m^{2} between microscale graphite contact surfaces while sliding under ambient conditions. This value is nearly 146 times higher than the maximum CCD of other SECs reported in literatures (0.12 GA/m^{2}). Meanwhile, the coefficient of friction for the graphite contact is less than 0.01 and the sliding interface is wear-free according to the Raman characterization, indicating the presence of the SSL state. Furthermore, we estimate the intrinsic CCD of single crystalline graphite to be 6.69 GA/m^{2} by measuring the scaling relation of CCD. Theoretical analysis reveals that the CCD is limited by thermal effect due to the Joule heat. Our results show the great potential of the SSL contacts to be used as SECs, such as micro- or nanocontact switches, conductive slip rings, or pantographs.

Inhomogeneous Fluid Transport Modeling in Dual-Scale Porous Media Considering Fluid-Solid Interactions.

Dynamics of fluid transport in ultratight reservoirs such as organic-rich shales differ from those in high-permeable reservoirs due to the complex nature of fluid transport and fluid-solid interaction in nanopores. We present a multiphase multicomponent transport model for primary production and gas injection in shale, considering the dual-scale porosity and intricate fluid-solid interactions. The pore space in the shale matrix is divided into macropores and nanopores based on pore size distribution. We employ density functional theory (DFT) to account for fluid-solid interactions and to compute the inhomogeneous fluid density distribution and phase behavior within a dual-scale matrix. The calculated fluid thermodynamic properties and transmissibility values are then integrated into the multiphase multicomponent transport model grounded in Maxwell-Stefan theory to simulate primary oil production from and gas injection into organic-rich shales. Our findings highlight DFT's adeptness in detailing the complex fluid inhomogeneities within nanopores─a critical concept that a cubic equation of state does not capture. Fluids within pores are categorized into confined and bulk states, restricted by a threshold pore width of 30 nm. Different compositions of fluid mixtures are observed in macropores and nanopores: heavier hydrocarbon components preferentially accumulate in nanopores due to their strong fluid-solid interactions. We utilize the developed model to simulate hydrocarbon production from an organic-rich shale matrix as well as CO2 injection into the matrix. During primary hydrocarbon production, strong fluid-solid interactions in nanopores impede the mobility of heavy components in the near-wall region, leading to their confinement. Consequently, heavy components mostly remain within the nanopores in the shale matrix during primary hydrocarbon production. During the CO2 injection process, the injected CO2 alters fluid composition within macropores and nanopores, promoting fluid redistribution. Injected CO2 engages in competitive fluid-solid interactions against intermediate hydrocarbons, successfully displacing a considerable number of these hydrocarbons from the nanopores.

Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

Midterm Outcomes of Multicenter Castor Single-Branch Stent Graft Use in the Treatment of Thoracic Aortic Diseases.

PURPOSE: The aim of this study was to evaluate the midterm efficacy and safety of a single-branch Castor stent graft in the treatment of thoracic aortic disease. MATERIALS AND METHODS: Clinical data of 106 patients with thoracic aortic disease treated with Castor single-branch stent graft at 3 centers were collected between May 2018 and June 2023. The indicators included technical success, stent-related complication, reintervention, retrograde dissection, endoleak, distal stent graft-induced entry (dSINE), branch patency, and mortality. The outcomes of the Castor stent graft for multibranch reconstruction above the arch was also analyzed. RESULTS: The technical success was 98.1% (104/106), while the surgical success was 93.4% (99/106). The reintervention was 2.8% (3/106), consisting of a case of retrograde type A dissection, an endoleak, and a dSINE. The retrograde dissection was 1.9% (2/106), while type I endoleak was 1.9% (2/106). The new dSINE was 2.8% (3/106), and the branch patency rate was 100%. The mortality was 1.9% (2/106). The mean follow-up time was 29.1±17.7 months. The 2-year post-surgery cumulative survival rate was 91.0%±3.1%, while the cumulative branch patency rate was 96.2%±2.2%. In addition, the cumulative freedom from stent-related reintervention rate was 93.2%±2.8%. A comparison showed no significant difference in the stent-related complication, branch patency, endoleak, reintervention, and mortality when the proximal end of the Castor stent graft was anchored to zones 1 or 2 of the aorta. CONCLUSION: Castor single-branch stent graft showed favorable early and midterm outcomes in the treatment of thoracic aortic disease. In addition, it was feasible to combine Castor stent graft with other advanced techniques for multibranch aortic arch reconstruction. CLINICAL IMPACT: The Castor single-branch stent graft was approval by the Chinese Food and Drug Administration in 2017. However, there were few studies on the mid-term outcomes for thoracic aortic disease after launching, which mainly focused on small single-center retrospective study. In the study, we assessed the mid-term outcomes of Castor stent graft through multi-center cases, Castor stent graft combined with other advanced techniques (such as fenestration and hybrid) for multi-branch reconstruction of aortic arch were also conducted. We found Castor single-branch stent graft showed favorable early and mid-term outcomes in the treatment of thoracic aortic disease. Additionally, it was feasible to combine Castor stent graft with other advanced technique for multi-branch aortic arch reconstruction. As an off-the-shelf branched stent graft with a wide range of models, it could be also used in most emergent situation. The Castor stent graft was expected to become more widely used in the future.

Co-inoculation of rhizobia and AMF improves growth, nutrient uptake, and cadmium resistance of black locust grown in sand culture.

Rhizobia and arbuscular mycorrhizal fungi (AMF) are symbiotic microorganisms important for plants grown in nutrient-deficient and heavy metal-contaminated soils. However, it remains unclear how plants respond to the coupled stress by heavy metal and nitrogen (N) deficiency under co-inoculation. Here, we investigated the synergistic effect of Mesorhizobium huakuii QD9 and Funneliformis mosseae on the response of black locust (Robinia pseudoacacia L.) grown in sand culture to cadmium (Cd) under N deficiency conditions. The results showed that single inoculation of AMF improved the growth and Cd resistance of black locust, co-inoculation improved the most. Compared to non-inoculated controls, co-inoculation mediated higher biomass and antioxidant enzyme activity, reduced oxidative stress, and promoted nodulation, mycorrhizal colonization, photosynthetic capacity, and N, P, Fe and Mg acquisition when exposed to Cd. This increase was significantly higher under N deficiency compared to N sufficiency. In addition, the uptake of Cd by co-inoculated black locust roots increased, but Cd translocation to the above-ground decreased under both N deficiency and sufficiency. Thus, in the tripartite symbiotic system, not merely metabolic processes but also Cd uptake increased under N deficiency. However, enhanced Cd detoxification in the roots and reduced allocation to the shoot likely prevent Cd toxicity and rather stimulated growth under these conditions.

Visible-light-induced C(sp3)-H bromination of 4-methylthiophene derivatives with HBr/H2O2.

A convenient method to synthesize ethyl 4-(bromomethyl)thiophene-3-carboxylate derivatives has been developed via a visible-light-induced radical process in good yields and with wide functional group tolerance under air conditions and at ambient temperature. The present protocol has the advantages of a high atom economy, easy purification, and environmental friendliness as it employs HBr as the bromine source and the cheap and low-toxic H2O2 as the oxidant. The synthetic utility of this method is demonstrated by a gram scale reaction and its application in the innovative synthesis of the clinical drug relugolix.

Strong mechanical anisotropy and an anisotropic Dirac state in 2D C5N3.

Two-dimensional (2D) carbon nitride materials have emerged as a versatile platform for the design of high-performance nanoelectronics, but strong anisotropy in 2D carbon nitrides has rarely been reported. In this work, a 2D carbon nitride with strong anisotropy composed of tetra-, penta-, and hexa-rings (named as TPH-C5N3) is proposed. This TPH-C5N3 exhibits both dynamical and mechanical stability. Furthermore, it also showcases remarkable thermal stability, reaching up to 2300 K, as evidenced by AIMD simulations conducted in an NVT environment utilizing the Nosé-Hoover thermostat. Significantly, TPH-C5N3 demonstrates high anisotropic ratios in its mechanical properties, positioning it as the frontrunner in the current carbon nitride systems. In addition, a Dirac cone with an anisotropic ratio of 55.8% and Fermi velocity of 7.26 × 105 m s-1 is revealed in TPH-C5N3. The nontrivial topological properties of TPH-C5N3 are demonstrated by a non-zero Z2 invariant and topologically protected edge states. Our study offers theoretical insights into an anisotropic 2D carbon nitride material, laying the groundwork for its design and synthesis.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Safety and Efficacy of Stent-Graft in the Treatment of Aortoiliac Artery Occlusive Disease: A Multicenter Study of Short-Term and Medium-Term Outcomes.

BACKGROUND: To evaluate the short-term and mid-term safety and efficacy of stent-graft compared with bare stents for treatment of aortoiliac occlusive disease (AIOD). METHODS: One hundred eighty three patients diagnosed with AIOD who received stent implantation at 3 vascular centers in north China between January 2019 and December 2021 were enrolled. Patients were divided into those undergoing stent-graft (Group A; n = 67) or bare stent (Group B; n = 116) implantation for retrospective cohort analysis. Efficacy was assessed as surgical success rate and rate of freedom from clinically driven target lesion reintervention at each follow-up time point. Safety was assessed by the rate of perioperative complication, major limb amputation, and aortoiliac artery-related mortality. RESULTS: There were no preoperative baseline differences between the 2 groups (P > 0.05). The surgical success was 91.04% for Group A, significantly higher than that for Group B (79.31%; P < 0.05). Incidence of perioperative complications was 2.98% for Group A, significantly lower than that for Group B (9.48%, P < 0.05), as was the rate of major limb amputation (A: 1.49% vs. B: 5.17%) and aortoiliac artery-related mortality (A: 1.49% vs. B: 4.31%), although these 2 indicators were not significantly different (P > 0.05). Follow-up rates were 91.8% for the total follow-up time of 3 years. Kaplan-Meier survival curve analysis gave significantly higher 1-year and 2-year freedom from clinically driven target lesion reintervention for Group A (98.51% and 95.52%) than for Group B (95.69% and 89.66%, P < 0.05). CONCLUSIONS: Stent-graft is more effective and safer than bare stent in the treatment of AIOD.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.