STAU1 exhibits a dual function by promoting amyloidogenesis and tau phosphorylation in cultured cells.

Staufen-1 (STAU1) is a double-stranded RNA-binding protein (RBP) involved in a variety of pathological conditions. In this study, we investigated the potential role of STAU1 in Alzheimer's disease (AD), in which two hallmarks are well-established as cerebral ß-amyloid protein (Aß) deposition and Tau-centered neurofibrillary tangles. We found that STAU1 protein level was significantly increased in cells that stably express full-length APP and the brain of APP/PS1 mice, an animal model of AD. STAU1 knockdown, as opposed to overexpression, significantly decreased the protein levels of ß-amyloid converting enzyme 1 (BACE1) and Aß. We further found that STAU1 extended the half-life of the BACE1 mRNA through binding to the 3' untranslated region (3'UTR). Transcriptome analysis revealed that STAU1 enhanced the expression of growth arrest and DNA damage 45 ß (GADD45B) upstream of P38 MAPK signaling, which contributed to STAU1-induced regulation of Tau phosphorylation at Ser396 and Thr181. Together, STAU1 promoted amyloidogenesis by inhibiting BACE1 mRNA decay, and augmented Tau phosphorylation through activating GADD45B in relation to P38 MAPK. Targeting STAU1 that acts on both amyloidogenesis and tauopathy may serve as an optimistic approach for AD treatment.

Enhanced rock weathering increased soil phosphorus availability and altered root phosphorus-acquisition strategies.

Enhanced rock weathering (ERW) has been proposed as a measure to enhance the carbon (C)-sequestration potential and fertility of soils. The effects of this practice on the soil phosphorus (P) pools and the general mechanisms affecting microbial P cycling, as well as plant P uptake are not well understood. Here, the impact of ERW on soil P availability and microbial P cycling functional groups and root P-acquisition traits were explored through a 2-year wollastonite field addition experiment in a tropical rubber plantation. The results show that ERW significantly increased soil microbial carbon-use efficiency and total P concentrations and indirectly increased soil P availability by enhancing organic P mobilization and mineralization of rhizosheath carboxylates and phosphatase, respectively. Also, ERW stimulated the activities of P-solubilizing (gcd, ppa and ppx) and mineralizing enzymes (phoADN and phnAPHLFXIM), thus contributing to the inorganic P solubilization and organic P mineralization. Accompanying the increase in soil P availability, the P-acquisition strategy of the rubber fine roots changed from do-it-yourself acquisition by roots to dependence on mycorrhizal collaboration and the release of root exudates. In addition, the direct effects of ERW on root P-acquisition traits (such as root diameter, specific root length, and mycorrhizal colonization rate) may also be related to changes in the pattern of belowground carbon investments in plants. Our study provides a new insight that ERW increases carbon-sequestration potential and P availability in tropical forests and profoundly affects belowground plant resource-use strategies.

Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.

AIMS: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. METHODS: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated. RESULTS: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 µg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group. CONCLUSION: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

Short-term regulation of TSFM level does not alter amyloidogenesis and mitochondrial function in type-specific cells.

BACKGROUND: Mitochondrial Ts translation elongation factor (TSFM) is an enzyme that catalyzes exchange of guanine nucleotides. By forming a complex with mitochondrial Tu translation elongation factor (TUFM), TSFM participates in mitochondrial protein translation. We have previously reported that TUFM regulates translation of beta-site APP cleaving enzyme 1 (BACE1) via ROS (reactive oxygen species)-dependent mechanism, suggesting a potential role in amyloid precursor protein (APP) processing associated with Alzheimer's disease (AD), which led to the speculation that TSFM may regulate APP processing in a similar way to TUFM. METHODS AND RESULTS: Here, we report that in cultured cells, knockdown or overexpression TSFM did not change protein levels in BACE1 and APP. Besides, the levels of cytoplasmic ROS and mitochondrial superoxide, in addition to ATP level, cell viability and mitochondrial membrane potential were not significantly altered by TSFM knockdown in the short term. Further transcriptome analysis revealed that expression of majority of mitochondrial genes were not remarkably changed by TSFM silencing. The possibility of TSFM involved in cardiomyopathy and cancer development was uncovered using bioinformatics analysis. CONCLUSIONS: Collectively, short-term regulation of TSFM level in cultured cells does not cause a significant change in proteins involved in APP processing, levels in ROS and ATP associated with mitochondrial function. Whereas our study could contribute to comprehend certain clinical features of TSFM mutations, the roles of TSFM in cardiomyopathy and cancer development might deserve further investigation.

[Characteristics，Sources，and Ozone-sensitive Species of VOCs in Four Seasons in Yuncheng].

Based on the one-year observational data of volatile organic compounds （VOCs） in an urban area of Yuncheng in 2021， the concentration， composition， sources， and ozone-sensitive species of VOCs in four seasons were analyzed. The results showed that the average annual concentration of VOCs was （32.1 ±24.2）×10-9， i.e.， at the national middle level. The seasonal concentrations of VOCs were in the order of： winter （46.3×10-9）> autumn （35.5×10-9）> spring （25.6×10-9）> summer （21.2×10-9）. Alkanes and OVOCs were the most dominant VOCs compounds， accounting for 69.0%-80.4% of TVOCs in Yuncheng. Affected by changes in source emissions， the proportion of OVOCs was higher in spring and summer （41%-43%）， whereas the proportion of alkanes was higher in autumn and winter （42%-43%）. Vehicle exhaust， LPG/NG， industrial production， and combustion sources were identified as the main sources of VOCs in Yuncheng. The largest contributors in the four seasons were vehicle exhaust （28.5% in spring）， secondary + combustion sources （29.0% in summer）， LPG/NG sources （30.4% in autumn）， and coal combustion （27.3% in winter）. The ozone formation was located in the transitional regime in summer and in the VOC-limited regime in other seasons. Ozone production was more sensitive to alkenes （isoprene， ethylene， and propene）， OVOCs （acetaldehyde and propanal）， and aromatics （xylene， toluene， and benzene）. Winter was more sensitive to ethylene， and the other seasons were more sensitive to isoprene. The primary emission sources related to these sensitive species should be reduced to achieve the goal of air quality improvement.

The small molecule raptinal can simultaneously induce apoptosis and inhibit PANX1 activity.

Discovery of new small molecules that can activate distinct programmed cell death pathway is of significant interest as a research tool and for the development of novel therapeutics for pathological conditions such as cancer and infectious diseases. The small molecule raptinal was discovered as a pro-apoptotic compound that can rapidly trigger apoptosis by promoting the release of cytochrome c from the mitochondria and subsequently activating the intrinsic apoptotic pathway. As raptinal is very effective at inducing apoptosis in a variety of different cell types in vitro and in vivo, it has been used in many studies investigating cell death as well as the clearance of dying cells. While examining raptinal as an apoptosis inducer, we unexpectedly identified that in addition to its pro-apoptotic activities, raptinal can also inhibit the activity of caspase-activated Pannexin 1 (PANX1), a ubiquitously expressed transmembrane channel that regulates many cell death-associated processes. By implementing numerous biochemical, cell biological and electrophysiological approaches, we discovered that raptinal can simultaneously induce apoptosis and inhibit PANX1 activity. Surprisingly, raptinal was found to inhibit cleavage-activated PANX1 via a mechanism distinct to other well-described PANX1 inhibitors such as carbenoxolone and trovafloxacin. Furthermore, raptinal also interfered with PANX1-regulated apoptotic processes including the release of the 'find-me' signal ATP, the formation of apoptotic cell-derived extracellular vesicles, as well as NLRP3 inflammasome activation. Taken together, these data identify raptinal as the first compound that can simultaneously induce apoptosis and inhibit PANX1 channels. This has broad implications for the use of raptinal in cell death studies as well as in the development new PANX1 inhibitors.

The efficacy of bevacizumab combined with platinum-containing chemotherapy in the treatment of advanced non-small cell lung cancer in China: a systematic review and meta-analysis of randomized clinical trials.

Background: Platinum-based dual-drug first-line chemotherapy is commonly employed in the treatment of patients with advanced non-small cell lung cancer (NSCLC), although its clinical efficacy is limited. Bevacizumab can antagonize vascular endothelial cell growth factor (VEGF), which inhibit tumor angiogenesis and prevent tumor invasion and development. However, a comprehensive meta-analysis evaluating the effectiveness and safety of combining bevacizumab with platinum-based chemotherapy in advanced NSCLC patients is lacking. Methods: Randomized controlled trials (RCTs) investigating the combination therapy of bevacizumab and platinum-based chemotherapy for treating advanced NSCLC were searched across six databases. Data on objective response rate (ORR), disease control rate (DCR), 1-year survival rate, 2-year survival rate, 3-year survival rate, VEGF levels, and side effects were synthesized. Relative risk degree (RR) along with 95% confidence interval (CI) was used as statistical analysis measures for binary outcomes while continuous variables were analyzed using mean difference (MD) along with 95% CI. Heterogeneity was evaluated by Chi-squared and I2 tests. If there was heterogeneity, subgroup analysis was performed. Sensitivity analysis of the main outcome measures and assessment of publication bias were also performed. Results: According to our screening criteria, a total of Forty-nine RCTs were included, involving data from 4268 patients. The results of this analysis showed that compared with platinum-containing chemotherapy alone, bevacizumab combined with platinum-containing chemotherapy significantly improved ORR (RR [95% CI], 1.53 [1.44, 1.63], p < 0.00001), DCR (RR [95% CI], 1.24 [1.19, 1.29], p < 0.0001), 1-year survival rate (RR [95% CI], 1.34 [1.15, 1.57], p = 0.0003), 2-year survival rate (RR [95% CI], 2.16 [1.35, 3.43], p = 0.001), 3-year survival rate (RR [95% CI], 2.00 [1.21, 3.30], p = 0.007). In addition, bevacizumab with platinum-containing chemotherapy observably decreased the VEGF levels (RR [95% CI], -67.35 [-91.46, -43.25], p < 0.00001). Conclusion: Combination therapy involving bevacizumab demonstrated improved antitumor effects compared to chemotherapy alone in terms of ORR, DCR, 1-year survival rate, 2-year survival rate, 3-year survival rate, and VEGF levels without an increased incidence of adverse reactions. These analyses' results can provide clinicians guidance when selecting appropriate treatments for patients diagnosed with advanced non-small cell lung cancer.

Fabrication of complexed nanostructure using AAO template for ultrasensitive SERS detection.

In the study of surface-enhanced Raman scattering (SERS) processes, a simple and fast approach is needed to ensure the large-scale preparation of SERS substrates. This article uses anodic aluminum oxide (AAO) as a template to assemble gold nanoparticles (Au NPs) into an ordered array. By changing the pore size of AAO and silanizing the pores, the number and density of Au NPs entering the pores through liquid-liquid two-phase self-assembly (LLSA) can be effectively regulated. Using Rh6G (Rhodamine 6G) and CV (Crystal Violet) molecules as probe molecules, substrate sensitivity was evaluated with an enhancement factor of up to 6.34 × 107. In addition, the uniformity of the substrate is good, with a relative standard deviation (RSD) of 9.94%, and the logarithmic concentration and the Raman signal presented significant linear correlations R2 was 0.997 and 0.985, respectively. The detection limit of the substrate for APM (aspartame) as a solvent is as low as 0.0078 g/L. Finally, the substrate was subjected to high sensitivity testing on two types of beverages containing APM sold, proving the practicality of the substrate. It is expected to achieve simple and rapid detection in food additive trace detection in the future.

Electroacupuncture ameliorates cognitive impairment in APP/PS1 mouse by modulating TFEB levels to relieve ALP dysfunction.

Recently, the underlying mechanisms of acupuncture on the effects of Alzheimer's disease (AD) treatment have not been fully elucidated. Defects in ALP (autophagy-lysosomal pathway) and TFEB (transcription factor EB) play critical roles in AD. Our previous studies have demonstrated that electroacupuncture (EA) can ameliorate both ß-amyloid (Aß) pathology and cognitive function in APP/PS1 mice. However, the effects of EA on the expression of ALP and TFEB and their potential mechanisms require further investigation. Twenty-eight male APP/PS1 mice were randomly divided into Tg and Tg + EA groups, and 14 C57BL/6 mice served as the wild-type (WT) group. After 1 week of adaptation to the living environment, mice in the Tg + EA group were restrained in mouse bags and received manual acupuncture at Baihui (GV20) acupoint and EA stimulation at bilateral Yongquan (KI1) acupoints, using the same restraint method for WT and Tg groups. The intervention was applied for 15 min each time, every other day, lasting for six weeks. After intervention, the spatial learning and memory of the mice was assessed using the Morris water maze test. Hippocampal Aß expression was detected by immunohistochemistry and ELISA. Transmission electron microscopy (TEM) was used to observe autophagic vacuoles and autolysosomes in the hippocampus. Immunofluorescence method was applied to examine the expression of TFEB in CA1 region of the hippocampus and the co-localization of CTSD or LAMP1 with Aß. Western blot analysis was performed to evaluate the changes of LC3, p62, CTSD, LAMP1, TFEB and n-TFEB (nuclear TFEB) in the hippocampus. The findings of behavioral assessment indicated that EA alleviated the cognitive impairment of APP/PS1 mice. Compared with the WT group, the Tg group showed significant cognitive decline and abnormalities in ALP and TFEB function (P < 0.01 or P < 0.05). However, these abnormal changes were alleviated in the Tg + EA group (P < 0.01 or P < 0.05). The Tg group also showed more senile plaques and ALP dysfunction features, compared with the WT group, and these changes were alleviated by EA. In conclusion, this study highlights that EA ameliorated Aß pathology-related cognitive impairments in the APP/PS1 model associated with ALP and TFEB dysfunction.

Isoliquiritigenin Containing PH Sensitive Micelles for Enhanced Anti-Colitis Activity.

Isoliquiritigenin (ISL) is known to have a variety of pharmacological activities, but its poor water solubility limits its application. In order to improve the bioavailability of ISL and its anti-colitis activity, this study aims to develop an effective drug delivery system loaded with ISL. In this study, ISL pH-sensitive micelles (ISL-M) were prepared by thin film hydration method. The micellar size (PS), polydispersity index (PDI), electrokinetic potential (ζ-potential), drug loading (DL), encapsulation rate (EE) and other physical parameters were characterized. The storage stability of ISL-M was tested, release in vitro and pharmacokinetic studies in rats were performed, and the anti-inflammatory effect of ISL-M on ulcerative colitis induced by dextran sulfate sodium (DSS) was evaluated. The results showed that PS, PDI, ZP, EE% and DL% of ISL-M were 151.15±1.04 nm, 0.092±0.014, -31.32±0.721 mV, 93.97±1.53 % and 8.42±0.34 %, respectively. Compared with unformulated ISL (F-ISL), the cumulative release rate of ISL-M in the three different media was significantly increased and showed a certain pH sensitivity. The area under drug curve (AUC0-t) and peak concentration (Cmax) of ISL-M group were 2.94 and 4.06 times higher than those of ISL group. In addition, ISL-M is expected to develop new methods for increasing the bioavailability and anti-inflammatory activity of ISL.

Risk Factors for Delirium Superimposed on Dementia in Elderly Patients in Comprehensive Ward.

OBJECTIVE: To investigate the incidence of delirium and its related risk factors in patients with senile dementia during hospitalization. METHODS: A retrospective analysis of clinical data of 157 patients over 65 with cognitive impairment who were hospitalized in the comprehensive ward from October 2019 to February 2023 was conducted. Patients were assigned into delirium and non-delirium groups according to whether they exhibited delirium during hospitalization. General information about the patients and Visual Analogue Scale (VAS) score, blood C-reactive protein level, and blood superoxide dismutase (SOD) level were recorded. Univariate analysis was used to identify potential risk factors for delirium, and factors with statistical significance were subjected to multivariate logistic regression analysis. A prediction line chart for delirium in elderly dementia patients was constructed using R 4.03 software, and the model was validated. RESULTS: Among the 157 patients with senile dementia, 42 patients exhibited delirium and 115 patients exhibited non-delirium. Multivariate logistic regression analysis showed that diabetes, cerebrovascular disease, VAS score ≥4 points, use of sedative drugs, and blood SOD <129 U/mL were independent risk factors for delirium during hospitalization in elderly dementia patients. A prediction nomogram was plotted based on the five risk factors, and receiver operating characteristic curve analysis presented an area under the curve of .875 (95% CI: .816-.934). The nomogram model was internally validated by the Bootstrap method, and the calibration curve showed good agreement between predicted and actual results. Hosmer-Lemeshow test demonstrated that the model had a good fit and high predictive ability. CONCLUSION: Diabetes, cerebrovascular disease, VAS ≥4 points, use of sedative drugs, and blood SOD <129 U/mL were independent risk factors for delirium in patients with senile dementia during hospitalization. The nomogram model had good accuracy and clinical application value for predicting delirium in this study.

A case report of a brain abscess due to prevotella oris and a review of the literature.

BACKGROUND: Brain abscesses caused by Prevotella oris are rarely reported. Here, we described a case of a brain infection caused by Prevotella oris that was detected by metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 63-year-old man with no medical history reported headache in the right frontotemporal region, fever, and intermittent diplopia. Magnetic resonance imaging (MRI) revealed abnormal signals and enhancement changes in the superior sellar region. mNGS testing showed that cerebrospinal fluid collected from the spine was positive for Prevotella oris. After receiving a combined treatment of antibiotic therapy, the patient recovered well. CONCLUSION: We reviewed the relevant literature and summarized the characteristics and prognosis of this type of bacterial infection to provide ideas for clinicians to diagnose and treat this disease.

The Surfactant Role on a Droplet Passing through a Constricted Microchannel in a Pressure-Driven Flow: A Lattice Boltzmann Study.

The role of surfactants in the flow of a droplet driven by a pressure gradient through a constricted microchannel is simulated by using our recently developed lattice Boltzmann method. We first study the surfactant role on a droplet flowing through a microchannel with a shrunken square section under different surfactant concentrations and capillary numbers (i.e., imposed pressure gradients). As the surfactant concentration increases, the droplet flow regime first changes from the flow regime I of the droplet getting stuck at the entrance of the constricted channel to the flow regime II of the droplet flowing through the constricted channel with breakup, and then to the flow regime III of the droplet flowing through the constricted channel without breakup. As the capillary number increases, the surfactant role on the number of mother droplets breaking up and the time of mother droplets completely flowing through the constricted section tend to decrease, suggesting that the surfactant effects are gradually weakened. Then, a phase diagram describing how the surfactant concentration and capillary number affect the droplet flow regime is presented. As the surfactant concentration increases, the critical capillary number that distinguishes droplet flow regimes I from II gradually decreases, while the critical capillary number that distinguishes droplet flow regimes II from III first increases and then decreases.

[Electroacupuncture at "Baihui"（GV20） and "Yongquan"（KI1） improves learning-memory ability of APP/PS1 double transgenic mice by regulating endosomal-lysosomal system].

OBJECTIVE: To explore the mechanism of electroacupuncture（EA） in improving learning-memory ability in Alzheimer's disease （AD） mice from the perspective of endosomal-lysosomal system. METHODS: Male APP/PS1 transgenic mice were randomly divided into model group and EA group （n=10 in each group） and 10 male C57BL/6 wild mice were taken as the normal group. EA （1 Hz/50 Hz, 1 mA） was applied at bilateral "Yongquan"（KI1） and acupuncture was applied at "Baihui" （GV20） for 15 min. The mice of the model and normal groups were subjected to restriction with the same method as those of the EA group for 15 min. The treatment was conducted once every other day for 6 weeks. The spatial learning-memory ability （shown by escape latency of place navigation test and the time of crossing the target platform and total swimming distance in the target quadrant in 1 min of spatial probe test ） was detected by Morris water maze test. The immunoactivity of senile plaques （SP） in the hippocampus tissue was detected by immunohistochemistry. The ultrastructural characters of hippocampal neurons were observed by transmission electron microscope, and the expression levels of Ras-related protein 5 （Rab5）, Ras-related protein 7 （Rab7） and cathepsin D （CTSD） in the hippocampus were detected by Western blot, separately. RESULTS: Compared with the normal group, the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD were significantly increased （P<0.05, P<0.01）, while the number of crossing the original platform and the total swimming distance in the platform quadrant were considerably reduced （P<0.05） in the model group. In contrast to the model group, the EA group had a marked decrease in the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD （P<0.05, P<0.01）, and a striking increase in the number of crossing the original platform and the swimming distance in the platform quadrant （P<0.05）. Results of transmission electron microscope showed an accumulation of endosome, lysosome, and endolysosomes in the hippocampal neurons in the model group, which was evidently milder in the EA group. CONCLUSION: EA of GV20 and KI1 can improve the learning-memory ability of AD mice, which may be related to its function in reducing hippocampal Aß deposition and down-regulating endosomal-lysosomal system activity.

Enhanced secondary organic aerosol formation during dust episodes by photochemical reactions in the winter in Wuhan.

To investigate the effect of frequently occurring mineral dust on the formation of secondary organic aerosol (SOA), 106 volatile organic compounds (VOCs), trace gas pollutants and chemical components of PM2.5 were measured continuously in January 2021 in Wuhan, Central China. The observation period was divided into two stages that included a haze period and a following dust period, based on the ratio of PM2.5 and PM10 concentrations. The average ratio of secondary organic carbon (SOC) to elemental carbon (EC) was 1.98 during the dust period, which was higher than that during the haze period (0.69). The contribution of SOA to PM2.5 also increased from 2.75% to 8.64%. The analysis of the relationships between the SOA and relative humidity (RH) and the odd oxygen (e.g., OX = O3 + NO2) levels suggested that photochemical reactions played a more important role in the enhancement of SOA production during the dust period than the aqueous-phase reactions. The heterogeneous photochemical production of OH radicals in the presence of metal oxides during the dust period was believed to be enhanced. Meanwhile, the ratios of trans-2-butene to cis-2-butene and m-/p-xylene to ethylbenzene (X/E) dropped significantly, confirming that stronger photochemical reactions occurred and SOA precursors formed efficiently. These results verified the laboratory findings that metal oxides in mineral dust could catalyse the oxidation of VOCs and induce higher SOA production.

A mid-infrared high-performance spectropolarimetry filter based on dual-mode independent modulation.

Spectropolarimetry detection provides multi-dimensional accurate information with broad applications from biomedicine to remote sensing. Existing methods for simultaneously obtaining spectra and polarizations are either large and complex systems or miniaturized devices with too low spectral resolution or poor polarization selectivity, which inherently generate cross-talk of substantial information. Here, we propose a compact and single-chip integrated high-performance mid-infrared spectropolarimetry filter (SPF), whose narrowband spectral and polarization characteristics can be independently modulated by different polarization modes. A SPF is designed with a polarization extinction ratio (ER) over 106, spectral resolution (SR, λ/Δλ) up to 822 and a transmission efficiency of 90% in the mid-infrared band. The experimental ER and SR are over 3 × 104 and up to 387 respectively with a transmission efficiency of 60%. These results agree well with the theoretical results and can accurately obtain spectral and polarization information simultaneously. This device has been used in tumor diagnostics to well distinguish striated muscle and rhabdomyosarcoma tissue for demonstration. It can be easily extended to different wavelength ranges and provides a new and powerful approach for multi-dimensional optical information acquisition, target detection and accurate identification.

The Impact of Environmental and Host Factors on Human Cystic Echinococcosis: A County-Level Modeling Study in Western China.

Human cystic echinococcosis (CE) is a parasitic disease caused by tapeworms from the Echinococcus granulosus genus, potentially affected by the environment and host animals. West China is one of the most endemic areas of human CE nation and worldwide. The current study identifies the crucial environmental and host factors of human CE prevalence in the Qinghai-Tibet Plateau and non-Qinghai-Tibet Plateau regions. An optimal county-level model was used to analyze the association between key factors and human CE prevalence within the Qinghai-Tibet Plateau. Geodetector analysis and multicollinearity tests identify key factors, and an optimal model is developed through generalized additive models. In the Qinghai-Tibet Plateau, four key factors were identified from the 88 variables, such as maximum annual precipitation (Pre), maximum summer normalized difference vegetation index (NDVI), Tibetan population rate (TibetanR), and positive rates of Echinococcus coproantigen in dogs (DogR). Based on the optimal model, a significant positive linear relationship was observed between maximum annual Pre and human CE prevalence. A probable U-shaped curve depicts the non-linear relationship between maximum summer NDVI and the human CE prevalence. Human CE prevalence possesses significant positive non-linear relationships with TibetanR and DogR. Human CE transmission is integrally affected by environmental and host factors. This explains the mechanism of human CE transmission based on the pathogen, host, and transmission framework. Therefore, the current study provides references and innovative ideas for preventing and controlling human CE in western China.

Mixed scaling deconstruction in vacuum membrane distillation for desulfurization wastewater treatment by a cascade strategy.

Mineral scaling is one key obstacle to membrane distillation in hypersaline wastewater desalination, but the scaling or fouling mechanism is poorly understood. Addressing this challenge required revealing the foulants layer formation process. In this work, the scaling process was deconstructed with a cascade strategy by stepwise changing the composition of the synthetic desulfurization wastewater. The flux decline curves presented a 3-stage mode in vacuum membrane distillation (VMD). Heterogeneous nucleation of CaMg(CO3)2, CaF2, and CaCO3 was the main incipient scaling mechanism. Mg-Si complex was the leading foulant in 2nd-stage, during which the scaling mechanism shifted from surface to bulk crystallization. The flux decreased sharply for the formation of a thick and compacted scaling layer by the bricklaying of CaSO4 and Mg-Si-BSA complexes in the 3rd-stage. Bulk crystallization was identified as the key scaling mechanism in VMD for the high salinity and concentration multiple. The organic matter had an anti-scaling effect by changing the bulk crystallization. Humic acids (HA) and colloidal silica also contributed to incipient scaling for the high affinity to membrane, bovine serum albumin (BSA) acting as the cement of Mg-Si complexes. Mg altered the Si scaling from polymerization to Mg-Si complex formation, which significantly influence the mixed scaling mechanism. This work deconstructed the mixed scaling process and illuminated the role of main foulants, filling in the knowledge gap on the mixed scaling mechanism in VMD for hypersaline wastewater treatment and recovery.

USP7 represses lineage differentiation genes in mouse embryonic stem cells by both catalytic and noncatalytic activities.

USP7, a ubiquitin-specific peptidase (USP), plays an important role in many cellular processes through its catalytic deubiquitination of various substrates. However, its nuclear function that shapes the transcriptional network in mouse embryonic stem cells (mESCs) remains poorly understood. We report that USP7 maintains mESC identity through both catalytic activity-dependent and -independent repression of lineage differentiation genes. Usp7 depletion attenuates SOX2 levels and derepresses lineage differentiation genes thereby compromising mESC pluripotency. Mechanistically, USP7 deubiquitinates and stabilizes SOX2 to repress mesoendodermal (ME) lineage genes. Moreover, USP7 assembles into RYBP-variant Polycomb repressive complex 1 and contributes to Polycomb chromatin-mediated repression of ME lineage genes in a catalytic activity-dependent manner. USP7 deficiency in its deubiquitination function is able to maintain RYBP binding to chromatin for repressing primitive endoderm-associated genes. Our study demonstrates that USP7 harbors both catalytic and noncatalytic activities to repress different lineage differentiation genes, thereby revealing a previously unrecognized role in controlling gene expression for maintaining mESC identity.

TNIP2 inhibits amyloidogenesis by regulating the 3'UTR of BACE1: An in vitro study.

TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-κB signaling and inhibit inflammatory response and apoptosis, and is also involved in RNA metabolism. In this study, we investigated the potential role of TNIP2 in amyloidogenesis critically associated with Alzheimer's disease (AD). We found a significant decline of TNIP2 protein level in both mouse and cell model of AD. In SH-SY5Y and HEK cells that stably express human full-length APP695 (SY5Y-APP and HEK-APP), TNIP2 overexpression decreased the protein levels of ß-secretase (BACE1) and C99, as well as Aß peptides (including Aß40 and Aß42), while those of α-secretase (ADAM10) and the related C83 remained unchanged. We further found that TNIP2 promoted the degradation of BACE1 mRNA and was able to bound to the 3' untranslated region (3'UTR) with the reduced luciferase activity. These results indicated that TNIP2 effectively inhibited amyloidogenic processing by regulating the 3'UTR-associated mRNA decay of BACE1.