Bioenergy recovery and carbon emissions benefits of short-term bio-thermophilic pretreatment on low organic sewage sludge anaerobic digestion: A pilot-scale study.

Sewage sludge in cities of Yangzi River Belt, China, generally exhibits a lower organic content and higher silt contentdue to leakage of drainage system, which caused low bioenergy recovery and carbon emission benefits in conventional anaerobic digestion (CAD). Therefore, this paper is on a pilot scale, a bio-thermophilic pretreatment anaerobic digestion (BTPAD) for low organic sludge (volatile solids (VS) of 4%) was operated with a long-term continuous flow of 200 days. The VS degradation rate and CH4 yield of BTPAD increased by 19.93% and 53.33%, respectively, compared to those of CAD. The analysis of organic compositions in sludge revealed that BTPAD mainly improved the hydrolysis of proteins in sludge. Further analysis of microbial community proportions by high-throughput sequencing revealed that the short-term bio-thermophilic pretreatment was enriched in Clostridiales, Coprothermobacter and Gelria, was capable of hydrolyzing acidified proteins, and provided more volatile fatty acid (VFA) for the subsequent reaction. Biome combined with fluorescence quantitative polymerase chain reaction (PCR) analysis showed that the number of bacteria with high methanogenic capacity in BTPAD was much higher than that in CAD during the medium temperature digestion stage, indicating that short-term bio-thermophilic pretreatment could provide better methanogenic conditions for BTPAD. Furthermore, the greenhouse gas emission footprint analysis showed that short-term bio-thermophilic pretreatment could reduce the carbon emission of sludge anaerobic digestion system by 19.18%.

Co-doped cryptomelane-type manganese oxide in situ grown on a nickel foam substrate for high humidity ozone decomposition.

Monolithic catalysts with excellent O3 catalytic decomposition performance were prepared by in situ loading of Co-doped KMn8O16 on the surface of nickel foam. The triple-layer structure with Co-doped KMn8O16/Ni6MnO8/Ni foam was grown spontaneously on the surface of nickel foam by tuning the molar ratio of KMnO4 to Co(NO3)2·6H2O precursors. Importantly, the formed Ni6MnO8 structure between KMn8O16 and nickel foam during in situ synthesis process effectively protected nickel foam from further etching, which significantly enhanced the reaction stability of catalyst. The optimum amount of Co doping in KMn8O16 was available when the molar ratio of Mn to Co species in the precursor solution was 2:1. And the Mn2Co1 catalyst had abundant oxygen vacancies and excellent hydrophobicity, thus creating outstanding O3 decomposition activity. The O3 conversion under dry conditions and relative humidity of 65%, 90% over a period of 5 hr was 100%, 94% and 80% with the space velocity of 28,000 hr-1, respectively. The in situ constructed Co-doped KMn8O16/Ni foam catalyst showed the advantages of low price and gradual applicability of the preparation process, which provided an opportunity for the design of monolithic catalyst for O3 catalytic decomposition.

Vibrotactile Foot Device for Freezing of Gait in Parkinson's Disease: A Pilot Study.

BACKGROUND: Vibrotactile stimulation has been studied in its efficacy of reducing freezing of gait (FOG) in patients with Parkinson's disease (PD). However, the results are still controversial. We evaluated the efficacy of a newly developed vibrotactile foot device on freezing severity and gait measures in PD patients with FOG. OBJECTIVE: To evaluate the efficacy of vibrotactile foot device on PD patients with FOG. METHODS: Thirty-three PD patients with FOG were examined during their "off" medication state. The efficacy of the vibrotactile foot device was evaluated using a gait protocol comprising walking trials with vibrotactile stimulation "off" and "on." Walking trials were videotaped for the offline rating by two movement disorder specialists. The Opal inertial sensor unit (128 Hz; Mobility Lab; APDM Inc., Portland, OR, USA) was used for quantitative gait analysis. RESULTS: The results demonstrated 33.1% reduction in number of FOG episodes (P < 0.001) and 32.6% reduction of freezing episodes (P < 0.001). Quantitative gait analysis showed a significant increase in step length (P = 0.033). A moderate negative correlation was observed between the change of percent time frozen and age (r = -0.415, P = 0.016). 73% of participants reported minimal to substantial improvement in walking with this vibrating stimulation delivered by the vibrotactile foot device. CONCLUSIONS: The vibrotactile foot device is an efficient device that could significantly reduce freezing severity and provide gait regulation to patients with PD experiencing frequent freezing. It could potentially be used in the home environment for improving the quality of life.

Impact of chronic sleep deprivation on male reproductive health: Insights from testicular and epididymal responses in mice.

BACKGROUND: Sleep deprivation (SD) can cause damage to the male reproductive system. However, the duration required for such damage and the specific sequence and severity of damage to the testis and epididymis remain unclear. OBJECTIVE: To investigate the effects of different durations of SD on different parts of the testis and epididymis caput, corpus, and cauda. METHODS: Adult ICR mice were randomly assigned to five groups: the SD group (SD for 18 h/day for 1, 2, 3, or 4 weeks), the SD + Vit E group (supplemented with Vit E 50 mg/kg/d during 4 weeks of SD, the SD+NS group (saline supplementation during 4 weeks of SD), the SD + RS group (5 weeks of recovery sleep after 4 weeks of SD), and a normal sleep control (Ctrl) group. Following the interventions, sperm parameters, testicular and epididymal histopathology, inflammatory response, and oxidative stress markers were compared between the groups. RESULTS: Compared to the Ctrl group, the SD group showed a decrease in sperm motility and concentration from SD 2 W and SD 3 W, respectively. Decreases in sperm concentration and motility were more pronounced in the cauda compared to the caput and corpus. Pathological damage was less severe in the epididymis caput than in the corpus and cauda. After 4 weeks of SD, inflammation and oxidative stress increased in both testes and epididymis. Both sleep recovery and vitamin E supplementation showed significant improvements, though they did not fully reach the level of the Ctrl group. CONCLUSION: Chronic SD for more than 2 weeks causes varying degrees of damage to the testis, epididymis caput, corpus, and cauda in male mice. This damage is not fully reversible after 5 weeks of sleep recovery and antioxidant stress treatment. These findings help us to identify and prevent SD damage to the male reproduction at an early stage.

Explore the Role of Frailty as a Contributor to the Association Between AT(N) Profiles and Cognition in Alzheimer's Disease.

Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent. Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty. Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database. Levels of cerebrospinal fluid amyloid-ß, p-tau, and t-tau were identified for AD-related pathology based on the amyloid-ß/tau/neurodegeneration (AT[N]) framework. Frailty was measured using a modified Frailty Index-11 (mFI-11). Regression and interaction models were utilized to assess the relationship among frailty, AT(N) profiles, and cognition. Moderation models analyzed the correlation between AT(N) profiles and cognition across three frailty levels. All analyses were corrected for age, sex, education, and APOEɛ4 status. Results: In this study, frailty (odds ratio [OR] = 1.71, p < 0.001) and AT(N) profiles (OR = 2.00, p < 0.001) were independently associated with cognitive status. The model fit was improved when frailty was added to the model examining the relationship between AT(N) profiles and cognition (p < 0.001). There was a significant interaction between frailty and AT(N) profiles in relation to cognitive status (OR = 1.12, pinteraction = 0.028). Comparable results were obtained when Mini-Mental State Examination scores were utilized as the measure of cognitive performance. The association between AT(N) profiles and cognition was stronger with the levels of frailty. Conclusions: Frailty may diminish patients' resilience to AD pathology and accelerate cognitive decline resulting from abnormal AD-related pathology. In summary, frailty contributes to elucidating the relationship between AD-related pathology and cognitive impairment.

Diagnostic value of 8-OHdG, 8-iso-PGF2α and TNF-α levels in blood for early carcinogenesis of erosive oral lichen planus.

BACKGROUND: Oral cancer has a high worldwide incidence and mortality rate showing an upward trend year by year, predominantly occurring in emerging countries. Oral squamous cell carcinoma (OSCC) is one of the main types of oral cancer, accounting for more than 90% of all cases in oral cancer. OBJECTIVE: To evaluate the diagnostic value of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-Prostaglandin F2alpha (8-iso-PGF2α) and tumor necrosis factor (TNF)-α as biomarkers in the early carcinogenesis of erosive oral lichen planus (EOLP) by measuring their levels in the blood of patients with EOLP and oral squamous cell carcinoma (OSCC). METHODS: A total of 69 patients were enrolled in this case-control study [including an OSCC group (n= 23), an EOLP group (n= 23), and an age- and gender-matched healthy control group (n= 23)]. Blood levels of 8-OHdG, 8-iso-PGF2α and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). Statistical differences in these indicators among the three groups were analyzed. RESULTS: Plasma levels of 8-OHdG and 8-iso-PGF2α in the OSCC group were significantly higher than those in both the EOLP group and the control group (all P< 0.05); no significant statistical difference was found between the EOLP group and the control group. Serum levels of TNF-α in both the OSCC and EOLP groups were elevated compared with the control group, showing significant differences among all three groups (all P< 0.05). Receiver operating characteristic (ROC) curves revealed that plasma 8-OHdG and 8-iso-PGF2α levels and serum TNF-α levels had diagnostic effects on early carcinogenesis in EOLP patients. When these indicators were combined for diagnosis, the diagnostic effect was enhanced, with an area under the ROC curve (AUC) values of 0.819. CONCLUSION: 8-OHdG, 8-iso-PGF2α and TNF-α may serve as biological indicators for monitoring the early carcinogenesis of EOLP, and the diagnostic effect was augmented when these indicators were combined.

Incremental prognostic value of cardiovascular magnetic resonance imaging in patients with severe LV dysfunction undergoing coronary artery bypass grafting.

BACKGROUND: Coronary artery disease (CAD) remains a significant global health issue, particularly when complicated by left ventricular ejection fraction (LVEF) < 35%. Although coronary artery bypass grafting (CABG) is recommended for such cases, the unclear prognosis necessitates further investigation. METHOD: This retrospective study aimed to determine whether cardiovascular magnetic resonance (CMR) imaging provides additional prognostic value in guiding effective clinical management. The study included patients with CAD and LVEF < 35% who underwent CABG surgery after enhanced CMR between March 2016 and March 2023. CMR was performed using a 3.0T scanner with steady-state free precession and phase-sensitive inversion recovery sequences. Prognostic analysis of clinical and CMR data was conducted, with the endpoint defined as cardiovascular death, revascularization, hospitalization for heart failure, or stroke. Statistical analysis included Student's t-test, chi-squared test, univariate and multivariate Cox regression analysis, receiver operating characteristic analysis, Harrell C statistical analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) analysis. RESULT: The study included 152 patients (mean age 58.6 ± 9.7 years; 138 men). During a mean follow-up of 2.0 years, 8 patients experienced cardiovascular death, while 1 case had revascularization, 13 had hospitalization for heart failure, and 11 had a stroke. Left atrial diameter index (LADi) (hazard ratio [HR], 1.08 [95% confidence interval (CI): 1.02-1.15]; P = 0.04) and late gadolinium enhancement (LGE) mass (HR, 1.03 [95% CI: 1.01-1.06]; P < 0.001) were associated with the endpoint, even after adjusting for multiple clinical variables. Adding LADi and LGE mass improved risk prediction for adverse events, as indicated by the C-index (0.738, p < 0.01), IDI (0.36), and NRI (0.13). CONCLUSION: Left atrial diameter index (LADi) and scar burden are valuable prognostic indicators in patients with LVEF < 35% undergoing CABG. They offer enhanced risk stratification beyond traditional clinical factors, highlighting their importance in guiding clinical management.

Highly efficient selective extraction of Li from spent LiNixCoyMnzO2 assisted with activated pyrite in a subcritical water system.

As the strategic importance of Li in the energy sector increases, selective Li extraction technology from spent lithium-ion batteries (LIBs) is attracting increasing attention. Current Li extraction processes typically suffer from lengthy procedures, high costs, and low efficiency. To improve the efficiency of Li extraction, a novel approach to achieve efficient Li recovery is proposed in this study, namely, reacting pyrite (FeS2) with LiNixCoyMnzO2 (NCM) powder in a subcritical water reduction (SWR) system. The reducing solvent environment created by the enhanced reaction of FeS2 with subcritical water converts the high-valent metals in NCM to a low-valent state, causing the collapse of the stable laminar structure and allowing Li+ to be released smoothly. After dual activation through mechanochemical and roasting processes, more than 99 % of Li is preferentially extracted under optimal conditions. Furthermore, Li+ in solution is converted into highly pure Li2CO3, while other metallic elements remain in the residue. Using inexpensive FeS2 for efficient Li extraction without adding additional chemical reagents is a promising approach for recovering spent LIBs.

Biochar with KMnO4-hematite modification promoted foxtail millet growth by alleviating soil Cd and Zn biotoxicity.

The excessive accumulation of Cd and Zn in soil poisons crops and threatens food safety. In this study, KMnO4-hematite modified biochar (MnFeB) was developed and applied to remediate weakly alkaline Cd-Zn contaminated soil, and the heavy metal immobilization effect, plant growth, and metal ion uptake of foxtail millet were studied. MnFeB application reduced the phytotoxicity of soil heavy metals; bioavailable acid-soluble Cd and Zn were reduced by 57.79% and 35.64%, respectively, whereas stable, non-bioavailable, residual Cd and Zn increased by 96.44% and 32.08%, respectively. The chlorophyll and total protein contents and the superoxide dismutase (SOD)activity were enhanced, whereas proline, malondialdehyde, the H2O2 content, glutathione reductase (GR), ascorbate peroxidase (APX) and catalase (CAT) activities were reduced. Accordingly, the expressions of GR, APX, and CAT were downregulated, whereas the expression of MnSOD was upregulated. In addition, MnFeB promoted the net photosynthetic rate and growth of foxtail millet plants. Furthermore, MnFeB reduced the levels of Cd and Zn in the stems, leaves, and grains, decreased the bioconcentration factor of Cd and Zn in shoots, and weakened the translocation of Cd and Zn from roots to shoots. Precipitation, complexation, oxidation-reduction, ion exchange, and π-π stacking interaction were the main Cd and Zn immobilization mechanisms, and MnFeB reduced the soil bacterial community diversity and the relative abundance of Proteobacteria and Planctomycetota. This study provides a feasible and effective remediation material for Cd- and Zn-contaminated soils.

Multi-layered computational gene networks by engineered tristate logics.

So far, biocomputation strictly follows traditional design principles of digital electronics, which could reach their limits when assembling gene circuits of higher complexity. Here, by creating genetic variants of tristate buffers instead of using conventional logic gates as basic signal processing units, we introduce a tristate-based logic synthesis (TriLoS) framework for resource-efficient design of multi-layered gene networks capable of performing complex Boolean calculus within single-cell populations. This sets the stage for simple, modular, and low-interference mapping of various arithmetic logics of interest and an effectively enlarged engineering space within single cells. We not only construct computational gene networks running full adder and full subtractor operations at a cellular level but also describe a treatment paradigm building on programmable cell-based therapeutics, allowing for adjustable and disease-specific drug secretion logics in vivo. This work could foster the evolution of modern biocomputers to progress toward unexplored applications in precision medicine.

T cell exhaustion in human cancers.

T cell exhaustion refers to a progressive state in which T cells become functionally impaired due to sustained antigenic stimulation, which is characterized by increased expression of immune inhibitory receptors, but weakened effector functions, reduced self-renewal capacity, altered epigenetics, transcriptional programme and metabolism. T cell exhaustion is one of the major causes leading to immune escape of cancer, creating an environment that supports tumor development and metastatic spread. In addition, T cell exhaustion plays a pivotal role to the efficacy of current immunotherapies for cancer. This review aims to provide a comprehensive view of roles of T cell exhaustion in cancer development and progression. We summerized the regulatory mechanisms that involved in T cell exhaustion, including transcription factors, epigenetic and metabolic reprogramming events, and various microenvironmental factors such as cytokines, microorganisms, and tumor autocrine substances. The paper also discussed the challenges posed by T cell exhaustion to cancer immunotherapies, including immune checkpoint blockade (ICB) therapies and chimeric antigen receptor T cell (CAR-T) therapy, highlightsing the obstacles encountered in ICB therapies and CAR-T therapies due to T cell exhaustion. Finally, the article provides an overview of current therapeutic options aimed to reversing or alleviating T cell exhaustion in ICB and CAR-T therapies. These therapeutic approaches seek to overcome T cell exhaustion and enhance the effectiveness of immunotherapies in treating tumors.

Bile acids attenuate hepatic inflammation during ischemia/reperfusion injury.

Background & Aims: Persistent cholestasis has been associated with poor prognosis after orthotopic liver transplantation. In this study, we aimed to investigate how the accumulation of tauro-beta-muricholic acid (TßMCA), resulting from the reprogramming of bile acid (BA) metabolism during liver ischemia/reperfusion (IR) stress, attenuates liver inflammation. Methods: Ingenuity Pathway Analysis was performed using transcriptome data from a murine hepatic IR model. Three different models of hepatic IR (liver warm IR, bile duct separation-IR, common bile duct ligation-IR) were employed. We generated adeno-associated virus-transfected mice and CD11b-DTR mice to assess the role of BAs in regulating the myeloid S1PR2-GSDMD axis. Hepatic BA levels were analyzed using targeted metabolomics. Finally, the correlation between the reprogramming of BA metabolism and hepatic S1PR2 levels was validated through RNA-seq of human liver transplant biopsies. Results: We found that BA metabolism underwent reprogramming in murine hepatocytes under IR stress, leading to increased synthesis of TßMCA, catalyzed by the enzyme CYP2C70. The levels of hepatic TßMCA were negatively correlated with the severity of hepatic inflammation, as indicated by the serum IL-1ß levels. Inhibition of hepatic CYP2C70 resulted in reduced TßMCA production, which subsequently increased serum IL-1ß levels and exacerbated IR injury. Moreover, our findings suggested that TßMCA could inhibit canonical inflammasome activation in macrophages and attenuate inflammatory responses in a myeloid-specific S1PR2-GSDMD-dependent manner. Additionally, Gly-ßMCA, a derivative of TßMCA, could effectively attenuate inflammatory injury in vivo and inhibit human macrophage pyroptosis in vitro. Conclusions: IR stress orchestrates hepatic BA metabolism to generate TßMCA, which attenuates hepatic inflammatory injury by inhibiting the myeloid S1PR2-GSDMD axis. Bile acids have immunomodulatory functions in liver reperfusion injury that may guide therapeutic strategies. Impact and implications: Our research reveals that liver ischemia-reperfusion stress triggers reprogramming of bile acid metabolism. This functions as an adaptive mechanism to mitigate inflammatory injury by regulating the S1PR2-GSDMD axis, thereby controlling the release of IL-1ß from macrophages. Our results highlight the crucial role of bile acids in regulating hepatocyte-immune cell crosstalk, which demonstrates an immunomodulatory function in liver reperfusion injury that may guide therapeutic strategies targeting bile acids and their receptors.

Switch to fixed-dose ainuovirine, lamivudine, and tenofovir DF versus elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV-1: the 48-week results of the SPRINT trial, a multi-centre, randomised, double-blind, active-controlled, phase 3, non-inferiority trial.

Background: We compared the efficacy and safety profiles of ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen. Methods: This study was a multi-centre, randomised, double-blind, active-controlled, non-inferiority trial recruiting PLWH from 10 clinical centres across China. Main inclusion criteria included age of 18-65 years (inclusive), and stably staying on an ARV regimen combining an NNRTI with a two-drug NRTI backbone for at least 12 months. Eligible participants must have maintained plasma HIV-1 ribonucleic acid (RNA) titre below 50 copies per mL confirmed on two successive tests at an interval of at least one month prior to randomisation. Participants were randomly assigned to receive ANV 150 mg plus lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate (TDF) 300 mg (ANV/3TC/TDF), or cobicistat (Cobi) 150 mg boosted EVG plus emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA titre at 50 copies per mL or above at week 48 using the US Food and Drug Administration snapshot algorithm, with a non-inferiority margin of 4 percentage points at a two-side 95% confidence level. This trial is active, but not recruiting, and is registered with Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100051605. Findings: Between October 2021 and February 2022, 923 patients were screened for eligibility, among whom 762 participants were randomized and had received at least one dose of ANV/3TC/TDF (n = 381) or EVG/Cobi/FTC/TAF (n = 381). At week 48, 7 (1.8%) participants on ANV/3TC/TDF and 6 (1.6%) participants on EVG/Cobi/FTC/TAF had plasma HIV-1 RNA titre at 50 copies per mL or above, including missing virological data within the time window (the Cochran-Mantel-Haenszel method, estimated treatment difference [ETD], 0.3%, 95% CI -1.6 to 2.1), establishing the non-inferiority of ANV/3TC/TDF to EVG/Cobi/FTC/TAF. The proportions of participants experiencing at least one treatment-emergent adverse events (AEs) were comparable between the two arms (97.6% versus 97.6%). A small proportion of participants discontinued study drug due to AEs (0.3% versus 0.3%). Serious AEs occurred in 11 (2.9%) participants on ANV/3TC/TDF and 9 (2.4%) participants on EVG/Cobi/FTC/TAF, respectively, none of which was considered related to study drug at the jurisdiction of the investigator. At week 48, participants on ANV/3TC/TDF showed a significantly less weight gain from baseline compared to those on EVG/Cobi/FTC/TAF (least square mean, 1.16 versus 2.05 kg, ETD -0.90 kg, 95% CI, -1.43 to -0.37). The changes in serum lipids from baseline also favoured ANV/3TC/TDF over EVG/Cobi/FTC/TAF. Interpretation: In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF. Funding: Jiangsu Aidea Pharmaceutical & the National "Thirteenth Five-year Period" Major Innovative Drugs Research and Development Key Project of the People's Republic of China Ministry of Science and Technology.

The Effect of Global Spinal Alignment on the Cervical Degeneration in Patients with Degenerative Lumbar Scoliosis.

PURPOSE: To elucidate the effect of global spinal alignment on the cervical degeneration in Patients with Degenerative Lumbar Scoliosis (DLS). METHODS: A total of 117 patients with DLS and 42 controls were analysed. DLS patients (study group) were categorized according to the SRS-Schwab classification. Patients with lumbar spinal stenosis were reviewed as a control group. Spinopelvic parameters were measured in cervical and full-length spine radiographs. Cervical degeneration was assessed using the Cervical Degeneration Index (CDI) scoring system. RESULTS: There were significant differences in C2-7 sagittal vertical axis, T1 Slope, thoracic kyphosis, Lumbar Lordosis (LL), and pelvic tilt between DLS and control groups. Although the DLS and control groups did not differ significantly with regard to CDI scores, a striking difference was noted when sagittal spinopelvic modifiers were considered individually. Patients with a Pelvic Incidence minus Lumbar Lordosis (PI-LL) modifier grade of ++ had significantly higher CDI scores than those with 0, and patients with a PI-LL or Sagittal Vertical Axis (SVA) modifier grade of ++ had significantly higher CDI scores than control group. Disk narrowing scores were highest in patients with a PI-LL modifier grades of ++ followed by those with +. Additionally, CDI scores were more associated with LL rather than cervical lordosis. CONCLUSIONS: Patients with DLS may be at greater risk of cervical spine degeneration, especially those with a PI-LL or SVA modifier grade of ++. Surgical strategy for DLS patients should be more carefully selected considering the restoration of LL.

Muscle-Inspired Formable Wood-Based Phase Change Materials.

Phase change materials (PCMs) are crucial for sustainable thermal management in energy-efficient construction and cold chain logistics, as they can store and release renewable thermal energy. However, traditional PCMs suffer from leakage and a loss of formability above their phase change temperatures, limiting their shape stability and versatility. Inspired by the muscle structure, formable PCMs with a hierarchical structure and solvent-responsive supramolecular networks based on polyvinyl alcohol (PVA)/wood composites are developed. The material, in its hydrated state, demonstrates low stiffness and pliability due to the weak hydrogen bonding between aligned wood fibers and PVA molecules. Through treatment of poly(ethylene glycol) (PEG) into the PVA/wood PEG gel (PEG/PVA/W) with strengthened hydrogen bonds, the resulting wood-based PCMs in the hard and melting states elevate the tensile stress from 10.14 to 80.86 MPa and the stiffness from 420 MPa to 4.8 GPa, making it 530 times stiffer than the PEG/PVA counterpart. Capable of morphing in response to solvent changes, these formable PCMs enable intricate designs for thermal management. Furthermore, supported by a comprehensive life cycle assessment, these shape-adaptable, recyclable, and biodegradable PCMs with lower environmental footprint present a sustainable alternative to conventional plastics and thermal management materials.

Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK.

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

Application of acid-activated near-infrared viscosity fluorescent probe targeting lysosomes in cancer visualization.

The higher viscosity and lower pH in lysosomes of cancer cells highlight their potential as biomarkers for cancer. Therefore, the development of acid-activated viscosity fluorescent probes is significant for the early diagnosis and treatment of cancer. Based on this, we have designed and synthesized a near-infrared fluorescent probe based on the 2-(2-hydroxyphenyl)benzothiazole (HBT) group, namely HBTH, to monitor the viscosity changes within lysosomes. It has been demonstrated that HBTH was extremely sensitive to viscosity, with a strong linear relationship between fluorescence intensity and log(viscosity) within the range of (logη) = 0-3.06 (a correlation coefficient of 0.98), proving its capability for quantitative viscosity measurement. In particular, the most obvious fluorescence enhancement of HBTH was only efficiently triggered by the combined effect of low pH and high viscosity. Furthermore, HBTH can rapidly localize to lysosomes by wash-free procedure at a low concentration (100 nM) and achieve high-fidelity imaging within 20 s. It can also monitor the dynamic processes of lysosomes in cells, viscosity changes under drug stimuli, and lysosomal behavior during mitophagy. Importantly, HBTH is capable of identifying tumors in tumor-bearing nude mice through in vivo imaging. These features make HBTH a powerful tool for the early diagnosis and treatment of cancer.

Serum CD44 levels in early pregnancy and its genetic variants for increased risk of gestational diabetes mellitus in Chinese pregnant women.

This study aimed to explore associations of serum cluster of differentiation 44 (CD44) level and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational weeks). Binary conditional logistic regressions were performed to examine associations of serum CD44 level and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 level in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 level and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12-3.40 & 1.95, 1.05-3.61). Furthermore, after adjustment for serum CD44 level, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98-3.48). In conclusion, serum CD44 level and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SIGNIFICANCE: Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 function plays a causal role in occurrence of GDM. Specifically, it remains unknown whether CD44 in early pregnancy can predict the later occurrence of GDM. In this study, we found that high serum CD44 and its genetic variants in early pregnancy were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms.

Significant association between methyl mercury level and latent tuberculosis infection risk: a cross-sectional study.

OBJECTIVES: This cross-sectional study aimed to explore the association between methyl mercury (MeHg) level and latent tuberculosis infection (LTBI) risk based on the data from National Health and Nutrition Examination Survey (NHANES 2011-2012). METHODS: A total of 5243 participants with 20 variables were enrolled. The importance of these variables on TB infection was first ranked by XGBoost and Random Forest methods. Then the association between MeHg level and infection risk was evaluated by restricted cubic spline, threshold effect, and generalized linear regression analyses. We also explored the factors correlated with the difference in MeHg level and finally conducted a mediation analysis to assess the mediating effect of MeHg in LTBI. RESULTS: 521 participants were experiencing the LTBI, and 12 variables showed the differences between infection and non-infection groups (all P < 0.05). Of them, MeHg presented the highest importance on the LTBI. Restricted cubic spline (RCS) next revealed a significant non-linear correlation of MeHg with LTBI (all P < 0.05). Adjusted regression models further indicated their independent association (all P < 0.05), and infection risk increased with the increase of MeHg (P for trend < 0.05). We also found a significant turning point, and their association was significantly observed when MeHg > 5.75 µg/L (P < 0.05). In addition, asthma history was related to the difference in MeHg levels between LTBI and non-LTBI groups. Mediation analysis found that MeHg level partially mediated the association of asthma and LTBI risk (all P < 0.05). CONCLUSIONS: Our study identified MeHg as an independent risk factor for LTBI risk. Their causal relationship needs more investigation to verify.

Developing a CRISPR/FrCas9 system for core promoter editing in rice.

Small mutations in the core promoter region of a gene may result in substantial changes in expression strengths. However, targeting TA-rich sequences of core promoters may pose a challenge for Cas9 variants such as SpCas9 and other G-rich PAM-compatible Cas9s. In this study, we engineered a unique FrCas9 system derived from Faecalibaculum rodentium for plant genome editing. Our findings indicate that this system is efficient in rice when the TATA sequence is used as a PAM. In addition, FrCas9 demonstrated activity against all 16 possible NNTA PAMs, achieving an efficiency of up to 35.3% in calli and generating homozygous or biallelic mutations in 31.3% of the T0 transgenic plants. A proof-of-concept experiment to examine editing of the rice WX core promoter confirmed that FrCas9-induced mutations could modify gene expression and amylose content. Multiplex mutations and deletions were produced by bidirectional editing, mediated by FrCas9, using a single palindromic TATA sequence as a PAM. Moreover, we developed FrCas9-derived base editors capable of programmable conversion between A·T and G·C pairs in plants. This study highlights a versatile FrCas9 toolset for plant core promoter editing, offering great potential for the fine-tuning of gene expression and creating of new germplasms. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00157-5.