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Prediction of drug-protein binding is critical for virtual drug screening. Many deep learning methods have been proposed to predict the drug-protein binding based on protein sequences and drug representation sequences. However, most existing methods extract features from protein and drug sequences separately. As a result, they can not learn the features characterizing the drug-protein interactions. In addition, the existing methods encode the protein (drug) sequence usually based on the assumption that each amino acid (atom) has the same contribution to the binding, ignoring different impacts of different amino acids (atoms) on the binding. However, the event of drug-protein binding usually occurs between conserved residue fragments in the protein sequence and atom fragments of the drug molecule. Therefore, a more comprehensive encoding strategy is required to extract information from the conserved fragments. In this paper, we propose a novel model, named FragDPI, to predict the drug-protein binding affinity. Unlike other methods, we encode the sequences based on the conserved fragments and encode the protein and drug into a unified vector. Moreover, we adopt a novel two-step training strategy to train FragDPI. The pre-training step is to learn the interactions between different fragments using unsupervised learning. The fine-tuning step is for predicting the binding affinities using supervised learning. The experiment results have illustrated the superiority of FragDPI.Supplementary material is available for this article at 10.1007/s11704-022-2163-9 and is accessible for authorized users.

Utilizing nanoscale zero valent iron (nZVI) to purify groundwater contaminated by arsenic species [As(III/V)] is an efficient technology, but the fast and severe aggregation of nZVI limits its practical applications. Herein, nZVI was anchored onto the mussel-inspired polydopamine-coated cellulose nanocrystals (CNCs-PDA-nZVI) as an efficient material for As groundwater remediation. In this set, the introduction of nZVI was expected to significantly enhance the arsenic removal property, while cellulose nanocrystals (CNCs) endowed nZVI with ultrahigh dispersibility. The batch results showed that the maximum As adsorption capacities of CNCs-PDA-nZVI (i.e., 333.3 mg g

Interface solar steam generation (ISSG) are charming for its applications in desalination and wastewater treatment. Biomass is an attractive substrate for utilizing solar vapor evaporators because of its natural pore structure and water transportability. Polymers like polydopamine (PDA) and polypyrrole (PPy) with broadband spectrum absorption are fascinating in photothermal materials (PTMs). Herein, PDA coated daikon-based (PDA-DK) and PPy coated daikon-based (PPy-DK) PTMs have been exploited for solar steam generation. When polyethylene foam (PEF) was used as an insulating layer to limit heat loss from the PTMs to bulk water, the evaporation rate of PDA-DK and PPy-DK was raised from 0.82 kg m–2 h–1 and 0.96 kg m–2 h–1 to 1.50 kg m–2 h–1 and 1.60 kg m–2 h–1, respectively. Meanwhile, the corresponding photothermal conversion efficiency was increased to 89.01% and 98.97%, which was increased by nearly 40% under 1-sun irradiation. In addition, PDA-DK and PPy-DK exhibited remarkable stability for the solar steam generation without significant change through 15 cycles. Furthermore, PDA-DK and PPy-DK could effectively desalt seawater and purify dyeing wastewater. All the results indicate that PDA-DK and PPy-DK have great potential in real-world applications for solar steam generation.

EBioMedicine 77, 103933 (2022). doi:10.1016/j.ebiom.2022.103933, Published by Elsevier, Amsterdam [u.a.]

The MIL-53(Al)-NH2 was designed to remove fluoride with hierarchical hollow morphology. It was used as an adsorbent for fluoride removal at a wide pH range (1-12) due to the positive zeta potential of MIL-53(Al)-NH2. The pH did not significantly influence the fluoride adsorption into MIL-53(Al)-NH2. However, the adsorbent indicated good adsorption capacity with maximum adsorption of 1070.6 mg g-1. Different adsorption kinetic and thermodynamic models were investigated for MIL-53(Al)-NH2. The adsorption of fluoride into MIL-53(Al)-NH2 followed the pseudo-second-order model and a well-fitted Langmuir model indicating chemical and monolayer adsorption process. When mass transfer model was used at initial concentrations of 100 ppm and 1000 ppm, the rates of conversion were 8.4 × 10-8 and 4.7 × 10-8 m s-1. Moreover, anions such as [Formula: see text], [Formula: see text], [Formula: see text], Cl-, and Br- also had less effect on the adsorption of fluoride. Also, experimental and theoretical calculations on adsorption mechanism of MIL-53(Al)-NH2 revealed that the material had good stability and regenerative capacity using alum as regenerant. In a nutshell, the dominant crystal face (1 0 1) and adsorption sites Al, O, and N combined well with F-, HF, and HF2- through density functional theory. It opens a good way of designing hollow MOFs for adsorbing contaminants in wastewater.

BackgroundAlthough rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care.ObjectiveTherefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI.MethodsData from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge.ResultsIn the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24).ConclusionsBased on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.

Heavy metal–contaminated sediment is a common environmental problem. In situ stabilization is an effective and low-cost method to remediate heavy metal–contaminated sediment. In this study, a red mud-based low-cost composite (RMM) was used to stabilize heavy metal–contaminated sediment. RMM was mixed with heavy metal–contaminated sediment at the doses of 0%, 1%, 3% and 5%. The CaCl2-extractable, DTPA-extractable, leachability (TCLP) and heavy metal fractions were analysed to evaluate the stabilization efficiency of RMM for heavy metals. The selected properties and microbial activities of the sediment were analysed to verify the safety of RMM to sediment. The results showed that RMM reduced the DTPA-, CaCl2- and TCLP-extractable heavy metals in sediment. At an RMM dose of 5%, DTPA-, CaCl2- and TCLP- extractable heavy metals were reduced by 7.60%, 72.34% and 69.24% for Pb; 18.20%, 76.7% and 23.57% for Cd; 32.7%, 96.50% and 49.64% for Zn; and 35.0%, 61.20% and 55.27% for Ni, respectively. TCLP- and DTPA-extractable Cu was reduced by 71.15% and 12.90%, respectively. In contrast, CaCl2-extractable Cu increased obviously after the application of RMM. RMM reduced the acid-soluble fraction of Zn by 6.99% and increased the residual fraction of Ni by 4.28%. However, the influence of RMM on the fractions of Pb, Cd and Cu was nonsignificant. In addition, the application of RMM increased the pH values of the sediment, and the microbial activity in the sediment was also obviously enhanced. These results indicated that RMM has great potential in the remediation of heavy metal–contaminated sediment.

International audience; Thermococcus gammatolerans is anaerobic euryarchaeon which grows optimally at 88 °C and its genome encodes a family B DNA polymerase (Tga PolB). Herein, we cloned the gene of Tga PolB, expressed and purified the gene product, and characterized the enzyme biochemically. The recombinant Tga PolB can efficiently synthesize DNA at high temperature, and retain 93% activity after heated at 95 °C for 1.0 h, suggesting that the enzyme is thermostable. Furthermore, the optimal pH for the enzyme activity was measured to be 7.0–9.0. Tga PolB activity is dependent on a divalent cation, among which magnesium ion is optimal. NaCl at low concentration stimulates the enzyme activity but at high concentration inhibits enzyme activity. Interestingly, Tga PolB is able to efficiently bypass uracil in DNA, which is distinct from other archaeal family B DNA pols. By contrast, Tga PolB is halted by an AP site in DNA, as observed in other archaeal family B DNA polymerases. Furthermore, Tga PolB extends the mismatched ends with reduced efficiencies. The enzyme possesses 3′-5′ exonuclease activity and this activity is inhibited by dNTPs. The DNA binding assays showed that Tga PolB can efficiently bind to ssDNA and primed DNA, and have a marked preference for primed DNA. Last, Tga PolB can be used in routine PCR.

Serum biomarkers are promising tools for evaluating patients following traumatic brain injury (TBI). However, their relationship with diffuse histopathology remains unclear. Additionally, translatability is a focus of neurotrauma research, however, studies using translational animal models are limited. Here, we evaluated associations between circulating biomarkers and acute thalamic histopathology in a translational micro pig model of mTBI. Serum samples were collected pre-injury, and 1 min-6 h following mTBI. Markers of neuronal injury (Ubiquitin Carboxy-terminal Hydrolase L1 [UCH-L1]), microglial/macrophage activation (Ionized calcium binding adaptor molecule-1 [Iba-1]) and interleukin-6 [IL-6]) and astrogliosis/astrocyte damage (glial fibrillary acidic protein [GFAP]) were measured. Axonal injury and histological features of neurons and glia were also investigated using immunofluorescent labeling and correlated to serum levels of the associated biomarkers. Consistent with prior experimental and human studies, GFAP, was highest at 6 h post-injury, while no substantial changes were observed in UCH-L1, Iba-1 or IL-6 over 6 h. This study also found promising associations between thalamic glial histological signatures and ensuing release of Iba-1 and GFAP into the circulation. Our findings suggest that in diffuse injury, monitoring serum Iba-1 and GFAP levels can provide clinically relevant insight into the underlying acute pathophysiology and biomarker release kinetics following mTBI, providing previously underappreciated diagnostic capability.

Traumatic brain injury (TBI) and can lead to persistent hypogonadotropic hypogonadism (PHH) and poor outcomes. We hypothesized that autoimmune and inflammatory mechanisms contribute to PHH pathogenesis. Men with moderate-to-severe TBI (n = 143) were compared with healthy men (n = 39). The TBI group provided blood samples 1–12 months post-injury (n = 1225). TBI and healthy control (n = 39) samples were assayed for testosterone (T) and luteinizing hormone (LH) to adjudicate PHH status. TBI samples 1–6 months post-injury and control samples were assayed for immunoglobulin M (IgM)/immunoglobulin G (IgG) anti-pituitary autoantibodies (APA) and anti-hypothalamus autoantibodies (AHA). Tissue antigen specificity for APA and AHA was confirmed via immunohistochemistry (IHC). IgM and IgG autoantibodies for glial fibrillary acid protein (GFAP) (AGA) were evaluated to gauge APA and AHA production as a generalized autoimmune response to TBI and to evaluate the specificity of APA and AHA to PHH status. An inflammatory marker panel was used to assess relationships to autoantibody profiles and PHH status. Fifty-one men with TBI (36%) had PHH. An age-related decline in T levels by both TBI and PHH status were observed. Injured men had higher APA IgM, APA IgG, AHA IgM, AHA IgG, AGA IgM, and AGA IgG than controls (p

Cathepsin B (CatB), a lysosomal cysteine protease, is important to brain function and may have dual utility as a peripheral biomarker of moderate-severe traumatic brain injury (TBI). The present study determined levels of pro- and mature (mat) CatB protein as well as cysteine protease activity within the frontal cortex (FC; proximal injury site), hippocampus (HC; distal injury site), and cerebral spinal fluid (CSF) collected 1–7 days after craniotomy and penetrating ballistic-like brain injury (PBBI) in rats. Values were compared with naïve controls. Further, the utility of CatB protein as a translational biomarker was determined in CSF derived from patients with severe TBI. Craniotomy increased matCatB levels in the FC and HC, and led to elevation of HC activity at day 7. PBBI caused an even greater elevation in matCatB within the FC and HC within 3–7 days. After PBBI, cysteine protease activity peaked at 3 days in the FC and was elevated at 1 day and 7 days, but not 3 days, in the HC. In rat CSF, proCatB, matCatB, and cysteine protease activity peaked at 3 days after craniotomy and PBBI. Addition of CA-074, a CatB-specific inhibitor, confirmed that protease activity was due to active matCatB in rat brain tissues and CSF at all time-points. In patients, CatB protein was detectable from 6 h through 10 days after TBI. Notably, CatB levels were significantly higher in CSF collected within 3 days after TBI compared with non-TBI controls. Collectively, this work indicates that CatB and its cysteine protease activity may serve as collective molecular signatures of TBI progression that differentially vary within both proximal and distal brain regions. CatB and its protease activity may have utility as a surrogate, translational biomarker of acute-subacute TBI.

Aim Primary thyroid lymphoma (PTL) is a rare malignant disease. Its prognosis depends on early diagnosis. The role of fine-needle aspiration (FNA), including smear cytology, cell block (CB) techniques, and immunohistochemistry (IHC) sections in the diagnosis of PTL is still unclear. Here we reported 19 cases of PTL and literature review to evaluate the diagnostic accuracy for lymphoma by cytology. Methods Our study retrospectively reviewed 19 patients diagnosed with PTL at the affiliated hospital of Southwest Medical University in China from June 2011 to May 2019. According to the Bethesda system for reporting thyroid cytopathology, the CB sections were evaluated for the presence of single tumor cells. IHC was performed on CB. Results The diagnostic accuracy for PTL of FNA, CB with smears, and the joint application of the three methods (FNA + CB + IHC) of our study with 19 cases was 68.4% (13/19), 83.3% (15/18), and 100% (17/17), respectively. Conclusion The present study demonstrates that FNA has low sensitivity in diagnosing PTL, but the joint application of FNA, CB, and IHC might provide high diagnostic accuracy for lymphoma and should be applied in all cases where the clinical suspicion is high regardless of the FNA findings.

We prospectively evaluated serum concentrations of glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), total tau (T-Tau), and neurofilament light (NF-L) from collegiate athletes at baseline and acutely after sport-related concussion (SRC) using the Quanterix Neurology 4Plex "B" (N4PB) multiplex assay. Uninjured controls were matched on age, sex, race, sport, and concussion history. Clinical outcomes included acute symptom severity, balance, rapid automated naming, computerized cognitive testing, and recovery duration. Baseline (

Guilin, a famous tourist city, is located in northeast Guangxi Province of Southwest China. However, recently, abnormal haze events occurred frequently in the winter. To characterize inorganic elements in PM2.5 and associated sources during a winter haze episode, 30 samples were collected from 6 sites in Guilin from December 16 to 20, 2016, and 24 inorganic elements were measured using an inductively coupled plasma mass spectrometer. The results showed that the sum of 24 inorganic elements varied from 5.47 ± 0.45 to 9.26 ± 0.73 μg m−3, and accounting for 6.81% ± 13.35% to 8.63% ± 15.05% of PM2.5 at all sites. Among them, crustal elements, including K, Ca, Na, Mg, Al, Fe, and Ti contributed approximately 82% ± 6%–90% ± 3%. Cluster results combined the coefficient of divergence and hierarchical cluster for inorganic elements and the sites showed that YS designated as the background site had obvious spatial heterogeneity, specially, mass concentration, and Igeo (index of geoaccumulation) values of Ni, Cr, Mo, and Ba were higher than those at the other five sites, which indicating that PM2.5 in Guilin was significantly affected by interregional transport. The results of source apportionment showed that Al, Ti, B, Fe, Ca, Mg, and Cr were derived from road and building dust, whereas Sb, As, and Hg originated from coal combustion, Co and V from vehicle emission (such as diesel and gasoline combustion), and other metals (Zn, Pb, Mn, Ba, Cu, Ni, Se, Cd, Mo, Tl, K, and Na) from coal combustion and industrial processes.

Metal-organic frameworks (MOFs) based membranes with superior mechanical properties are of particular interest in purification, separation, and catalysis. Nevertheless, their fabrication still remains a grand challenge. Here, fungus hyphae (Mucor) were used as a robust scaffold to load the MOFs and induced the formation of porous and flexible membranes. ZIF-8 was used as a representative of MOFs. The ZIF-8@Mucor membrane was formed by the in-situ growth of ZIF-8 on hyphae and then a vacuum filtration of the ZIF-8/hyphae composite. ZIF-8 was effectively dispersed on the ZIF-8@Mucor membrane, and the shear modulus of ZIF-8@Mucor-3 was 864 MPa by calculation. The ZIF-8@Mucor membrane exhibited promising properties for adsorption application to remove the highly toxic Pb2+. The adsorption capacity of this membrane was as high as 1443.29 mg/g. Results from dynamic adsorption indicated that the penetration concentration of Pb2+ ions was less than 5% of the original level before 80 min whereas after 160 min, penetration concentration of Pb2+ ions was more than 90%. This study would open a new way of how to synthesize composite MOFs/bacterial membranes for energy and environment purposes.

The lack of blood-brain barrier (BBB) penetrating ability has hindered the delivery of many therapeutic agents for tauopathy treatment. In this study, we report the synthesis of a circular bifunctional aptamer to enhance the in vivo BBB penetration for better tauopathy therapy. The circular aptamer consists of one reported transferrin receptor (TfR) aptamer to facilitate TfR-aptamer recognition-induced transcytosis across BBB endothelial cells, and one Tau protein aptamer that we recently selected to inhibit Tau phosphorylation and other tauopathy-related pathological events in the brain. This novel circular Tau-TfR bifunctional aptamer displays significantly improved plasma stability and brain exposure, as well as the ability to disrupt tauopathy and improve traumatic brain injury (TBI)-induced cognitive/memory deficits in vivo, providing important proof-of-principle evidence that circular Tau-TfR aptamer can be further developed into diagnostic and therapeutic candidates for tauopathies.

Aim: KRAS SNPs may increase KRAS transcription and KRAS levels. SNPs of KRAS 3′UTR can affect carcinoma risk and prognosis. Materials & methods: The rs8720 and rs7960917 in KRAS 3′UTR for colorectal carcinoma (CRC) risk and survival were investigated in a case–control study. Association between SNPs and CRC risk, survival analysis were analyzed by an unconditional logistic regression model, log-rank test, Kaplan–Meier estimation, Cox regression model and one-way analysis of variance. Results & conclusion: The genotype CT of rs8720 was significantly increased risk of CRC, decreased overall survival and event-free survival, and KRAS mRNA and protein expressions were significantly increased in individuals with rs8720 CT, TT genotype. rs8720 may be an important factor in CRC development and prognosis.

A 5-day PM2.5 sampling campaign was conducted during a typical haze episode from December 16 to 20, 2016, at five urban sites and one background site in Guilin, a famous tourist city in Southern China. A total of 30 PM2.5 samples were collected, and water-soluble inorganic ions (WSII) (SO42−, NO3−, NH4+, Ca2+, K+, Cl−, Na+, and Mg2+) were determined using ion chromatography. Correlation analysis, principal component analysis, and coefficient of divergence were applied to identify the formation mechanisms of secondary inorganic ions, potential sources, and spatial distribution of WSII. The average mass concentrations of PM2.5 at each sampling site were 71.6–127.85 μg m−3, which were more than the National Ambient Air Quality Standard (GB3095-2012, GradeII (35 μg m−3)) in China. SO42− NO3−, and NH4+ were the major WSII, accounting for 34.43–40.59% of PM2.5 mass. NO3−/SO42− ratio revealed that stationary sources-induced PM2.5 was still remarkable. Cl−/Na+ ratio and their strong correlation (r = 0.824) indicated that atmospheric transport from outside urban region played an effective role during the haze episode. Spatial variations of WSII are not pronounced at five urban sites except the background site. High relative humidity and O3 contributed to evidently influence the transformation of SO2 to SO42− but not obvious to NOx oxidation. Finally, the major sources of WSII are identified as the mixture of sea salt, coal combustion, biomass burning, vehicle exhaust and agricultural emissions (66.892%), and fugitive sources (19.7%).

Based on Chinese General Social Survey(CGSS) data, this paper selects ten variables, including height, gender, household registration, and age. Through the statistical analysis of 57,574 survey samples, this study finds that the average height of China’s population has increased by more than 10 cm in the past 100 years. Among the findings, the data indicate the average height of men born after the 1990s is 11 cm taller than that of men born after the 1920s, which has now reached 173 cm, and that the height of women is 10.93 cm taller, averaging 163 cm. The average height of the Chinese population reflects significant differences in gender, region or province, urbanity and rurality, and nationality, among other variables. The average height of men and women gradually increases with the increase of geographical latitude. Some economically developed southern provinces approach the average height of the North. This paper predicts that the average height of the newborn population will continue to have inertial growth in the next 20 years, and the newborn male population will reach the World Health Organization’s ideal height standard of 176.5 cm by 2030. The analysis suggests that geographic latitude and heredity are the determinants of body development. Geographical latitude difference is a super-variable for human mitochondria to regulate the proportion of heat outflow and ATP transformation. Historically, the population living in high-latitude areas of China migrates to economically developed low-latitude provinces such as Shanghai, Jiangsu, Zhejiang, and Guangdong, which is the main reason why the per capita height in these areas is significantly taller than that in other southern provinces.

The rapid increase of metabolomics has led to an increasing focus on metabolic pathway modeling and reconstruction. In particular, reconstructing an organism's metabolic network based on its genome sequence is a key challenge in systems biology. The method used to address this problem predicts the presence or absence of metabolic pathways from known pathways in a reference database. However, this method is based on manual metabolic pathway construction and cannot be used for large genome sequencing data. To address such problems, we apply a supervised machine learning approach consisting of deep neural networks to learn feature representations of metabolic pathways and feed these representations into random forests to predict metabolic pathways. The supervised learning model, DeepRF, predicts all known and unknown metabolic pathways in an organism. Evaluation of DeepRF on over 318,016 instances shows that the model can predict metabolic pathways with high-performance metrics accuracy (97%), recall (95%), and precision (99%). Comparing DeepRF with other methods in the literature shows that DeepRF produces more reliable results than other methods.

Multi-metal contaminated soil, such as Cr(VI), Cu(II), and Co(II), still challenge the environmental remediation. In this work, zerovalent iron-loaded hydroxyapatite (ZVI/HAP) was first applied to simultaneously adsorb multi-metal in contaminated soil. During the remediation, the co-existing Cu(II), Ni(II), and Co(II) were adsorbed and precipitated onto ZVI/HAP. This "spontaneous deposition" simultaneously achieved the adsorption of the cationic metals and improved the isoelectric point of ZVI/HAP to 4.83 from 1.59, thus significantly alleviating the electronegativity to enhance the capture and reduction efficiency of Cr(VI). The application of ZVI/HAP resulted in the reduction of more than 99% of total Cr(VI) in contaminated soil, and the almost complete adsorption of water-soluble and DTPA-extractable Cu, Ni and Co within 20 d. Based on the sequential extraction and risk reduction assessment, soil Cr, Cu, Ni, and Co speciation was transformed from an unstable state (exchangeable and carbonate-bound fractions) to a relatively stable state, reducing the risk of heavy metals in contaminated soil significantly. This study developed an efficient strategy for the remediation of multi-metal contaminated soil.

Uranium is well-known to have serious adverse effects on the ecological environment and human health. Bioremediation stands out among many remediation methods owing to its being economically feasible and environmentally friendly. This study reported a great promising strategy for eliminating uranium by Stenotrophomonas sp. CICC 23833 in the aquatic environment. The bacterium demonstrated excellent uranium adsorption capacity (q

Background: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury. Methods: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0–30), we obtained a standardised value (range 0–1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182. Findings: 2993 participants (median age was 51 years [IQR 30–67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03–0·15), with a median score of 0·17 (0·08–0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02–1·04; p

Background Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome. Methods We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R-2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure. Findings Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0 center dot 014 (95% CI 0 center dot 009-0 center dot 020) and R-2 by 4 center dot 9% (3 center dot 6-6 center dot 5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R-2 of 48-65% for IMPACT and 30-34% for CRASH prognostic models. Interpretation Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models.

This study aims to examine the cytotoxicity mechanisms of synthetic cathinone (bath salts) on rat primary cultured neurons and primary astroglial cells, and to assess their neurobehavioral effects on mice. We administered methylenedioxypyrovalerone (MDPV) to both rat primary cultured neurons and primary astroglial cells to assess cell injury. We also analyzed the effects of MDPV on these cell cultures using immunocytochemistry. We utilized western blotting to assess the breakdown of αII-spectrin and glial fibrillary acidic protein (GFAP) induced by MDPV. The western blotting experiment also included calpain and caspase inhibitors (SNJ1945 and Z-D-DCB, respectively) and pro-apoptotic and pro-necrotic agents (Staurosporine and calcium ionophore A23187, respectively). Lastly, we assessed MDPV’s effects on behavioral effects using rotarod, locomotor activity, elevated plus maze, Morris water maze, forced swimming, and open field tests. MDPV caused a dose-dependent release of LDH in both cerebrocortical neuron-astroglia mixed cultures and primary astroglial cultures. MDPV also caused neurite breakages and astroglial process retraction on immunocytochemistry. Lastly, MDPV induced αII-spectrin breakdown in western blotting experiments. Co-administration of calpain and caspase inhibitors reduced the degradation of αII-spectrin and GFAP. MDPV administration also increased anxiety-like behavior and locomotor activity in the mice. Synthetic cathinones, which share structural similarities with methamphetamine, also induce significant neurotoxic effects and neurobehavioral effects on rodent models. These neurotoxic effects are likely mediated by calpain and caspase-induced apoptosis and necrosis, while astroglial death is likely only due to calpain activation. Therefore, further research may focus on pharmacological interventions targeting these pathways to mitigate the cytotoxic impact of cathinones in humans.

Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4–8) were included, and all patients received an initial loading dose of 2.5 mg/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5 mg/kg/day whereas the subsequent 6 patients received 10 mg/kg/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood–brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.

A superb adsorbent for Cr(VI) removal with a high adsorption capacity and acidic resistance was facilely synthesized via in situ hydrothermal cross-linking and reduction reaction of poly-Schiff base using m-phenylenediamine and glutaraldehyde as feedstock. The hydrothermal process effectively facilitated the condensation between aldehyde and amine group to strengthen the chemical structure by cross-linking the polymeric chains. Morphological evolution of the polymer via disaggregation and reassembly to finally form regular core–shell configuration was observed. The produced nanoparticles possess the excellent adsorption performance (833.3 mg g−1), far beyond most of the reported adsorbents, and exhibit fine reusability. The possible adsorption mechanism can be attributed to Cr(VI) electrostatic adsorption followed by redox reaction and chelation.

Penetrating traumatic brain injury (pTBI) often occurs with systemic insults such as hemorrhagic shock (HS) and hypoxemic (HX). This study examines rat models of penetrating ballistic-like brain injury (PBBI) and HX+HS to assess whether the blood levels of brain and systemic response biomarkers phosphorylated neurofilament-heavy protein (pNF-H), neurofilament-light protein (NF-L), αII-spectrin, heat shock protein (HSP70), and high mobility group box 1 protein (HMGB1) can distinguish pTBI from systemic insults and guide in pTBI diagnosis, prognosis, and monitoring. Thirty rats were randomly assigned to sham, PBBI, HS+HX, and PBBI+HS+HX groups. PBBI and sham groups underwent craniotomy with and without probe insertion and balloon expansion, respectively. HX and HS was then simulated by blood withdrawal and fraction of inspired oxygen (FIO2) reduction. Biomarker serum concentrations were determined at one (D1) and two (D2) days post-injury with enzyme-linked immunosorbent assay (ELISA) methods. Axonal injury-linked biomarkers pNF-H and NF-L serum levels in PBBI groups were higher than those in sham and HX+HS groups at D1 and D2 post-injury. The same was true for PBBI+HX+HS compared with sham (D2 only for pNF-H) and HX+HS groups. However, pNF-H and NF-L levels in PBBI+HX+HS groups were not different than their PBBI counterparts. At D1, αII-spectrin levels in the HX+HS and PBBI+HS+HX groups were higher than the sham groups. αII-spectrin levels in the HX+HS group were higher than the PBBI group. This suggests HX+HS as the common insult driving αII-spectrin elevations. In conclusion, pNF-H and NF-L may serve as specific serum biomarkers of pTBI in the presence or absence of systemic insults. αII-spectrin may be a sensitive acute biomarker in detecting systemic insults occurring alone or with pTBI.

Increasing attention is now being paid to the important role played by autophagic flux in maintaining normal blood vessel walls. Endothelial cell dysfunction initiates the development of atherosclerosis. In the endothelium, a variety of critical triggers ranging from shear stress to circulating blood lipids promote autophagy. Furthermore, emerging evidence links autophagy to a range of important physiological functions such as redox homeostasis, lipid metabolism, and the secretion of vasomodulatory substances that determine the life and death of endothelial cells. Thus, the promotion of autophagy in endothelial cells may have the potential for treating atherosclerosis. This paper reviews the role of endothelial cells in the pathogenesis of atherosclerosis and explores the molecular mechanisms involved in atherosclerosis development.

Snapshot channeled imaging spectropolarimetry (SCISP), which can achieve spectral and polarization imaging without scanning (a single exposure), is a promising optical technique. As Fourier transform is used to reconstruct information, SCISP has its inherent limitations such as channel crosstalk, resolution and accuracy drop, the complex phase calibration, et al. To overcome these drawbacks, a nonlinear technique based on neural networks (NNs) is introduced to replace the role of Fourier reconstruction. Herein, abundant spectral and polarization datasets were built through specially designed generators. The established NNs can effectively learn the forward conversion procedure through minimizing a loss function, subsequently enabling a stable output containing spectral, polarization, and spatial information. The utility and reliability of the proposed technique is confirmed by experiments, which are proved to maintain high spectral and polarization accuracy.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor developing from the esophageal squamous epithelium, and is the most common histological subtype of esophageal cancer (EC). EC ranks 10th in morbidity and sixth in mortality worldwide. The morbidity and mortality rates in China are both higher than the world average. Current treatments of ESCC are surgical treatment, radiotherapy, and chemotherapy. Neoadjuvant chemoradiotherapy plus surgical resection is recommended for advanced patients. However, it does not work in the significant promotion of overall survival (OS) after such therapy. Research on targeted therapy in ESCC mainly focus on EGFR and PD-1, but neither of the targeted drugs can significantly improve the 3-year and 5-year survival rates of disease. Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is an important survival pathway in tumor cells, associated with its aggressive growth and malignant progression. Specifically, proliferation, apoptosis, autophagy, and so on. Related genetic alterations of this pathway have been investigated in ESCC, such as PI3K, AKT and mTOR-rpS6K. Therefore, the PI3K/AKT/mTOR pathway seems to have the capability to serve as research hotspot in the future. Currently, various inhibitors are being tested in cells, animals, and clinical trials, which targeting at different parts of this pathway. In this work, we reviewed the research progress on the PI3K/AKT/mTOR pathway how to influence biological behaviors in ESCC, and discussed the interaction between signals downstream of this pathway, especially eukaryotic translation initiation factors (eIFs) and the development and progression of ESCC, to provide reference for the identification of new therapeutic targets in ESCC.

Background Previous studies reported that BATF played an important role in the progression of various cancers, but no report had been found on clear cell renal cell carcinoma(ccRCC). So we investigated the effects of BATF on the progression of ccRCC. Methods In this study, using TCGA-KIRC database from the Cancer Genome Atlas to analyze the differential genes of BATF in ccRCC ; using immunohistochemistry to detect BATF expression in 75 ccRCC tumorous and 28 nontumorous tissues, and investigate its relationship with clinicopathological parameters. Moreover, we constructed the cell lines of BATF overexpression and knockout in Caki-1and 786-0 ccRCC cell lines and confirmed by western blot. CCK8 assay was used to evaluated the cell viability and using EdU staining to detect cell proliferation; using Transwell experiment to investigate the affection of BATF in ccRCC cell migration. Westernblot was used to detect the phosphorylation of PI3K/AKT/mTOR. Results These results revealed that BATF expression in ccRCC tumorous was significantly higher compared with that in adjacent nontumorous tissues and was significantly correlated with T stage, Fuhrman grade, Tumor necrosis and status. In addiditon, BATF overexpression significantly inhibited the viability, proliferation and migration of the two cell lines. More importantly, using westernblot showed that silencing BATF significantly increased the level of phosphorylated AKT, PI3K and mTOR, while BATF overexpression decreased phosphorylation that involved in the PI3K/Akt/mTOR signaling pathway. Conclusions Our findings demonstrate that BATF plays an important role in the progression of ccRCC and it may act as an tumor supressor gene to inhibit the progression of ccRCC through regulating the PI3K/Akt/mTOR signaling pathway.

INTRODUCTION Traumatic brain injury (TBI) is a major global health issue, resulting in debilitating consequences to families, communities, and health-care systems. Prior research has found that biomarkers aid in the pathophysiological characterization and diagnosis of TBI. Significantly, the FDA has recently cleared both a bench-top assay and a rapid point-of-care assays of tandem biomarker (UCH-L1/GFAP)-based blood test to aid in the diagnosis mTBI patients. With the global necessity of TBI biomarkers research, several major consortium multicenter observational studies with biosample collection and biomarker analysis have been created in the USA, Europe, and Canada. As each geographical region regulates its data and findings, the International Initiative for Traumatic Brain Injury Research (InTBIR) was formed to facilitate data integration and dissemination across these consortia. AREAS COVERED This paper covers heavily investigated TBI biomarkers and emerging non-protein markers. Finally, we analyze the regulatory pathways for converting promising TBI biomarkers into approved in-vitro diagnostic tests in the United States, European Union, and Canada. EXPERT OPINION TBI biomarker research has significantly advanced in the last decade. The recent approval of an iSTAT point of care test to detect mild TBI has paved the way for future biomarker clearance and appropriate clinical use across the globe.

Strongly alkaline high Cr(VI) contaminated (SAHCR) soil poses a high risk to the environment and public health, yet lacks rapid and efficient remediation technology. In this study, a novel approach combining microwave irradiation with zerovalent iron/pyrite (FeS

Soil moisture plays an important role in the land surface model. In this paper, a method of using VV polarization Sentinel-1 SAR and Landsat optical data to retrieve soil moisture data was proposed by combining the water cloud model (WCM) and the deep belief network (DBN). Since the simple combination of training data in the neural network cannot effectively improve the accuracy of the soil moisture inversion results, a WCM physical model was used to eliminate the effect of vegetation cover on the ground backscatter, in order to obtain the bare soil backscatter coefficient. This improved the correlation of ground soil backscatter characteristics with soil moisture. A DBN soil moisture inversion model based on the bare soil backscatter coefficients as the foundation training data combined with radar incidence angle and terrain factors obtained good inversion results. Studies in the Naqu area of the Tibetan Plateau showed that vegetation cover had a significant effect on the soil moisture, and the goodness of fit (R2) between the backscatter coefficient and soil moisture before and after the elimination of vegetation cover was 0.38 and 0.50, respectively. The correlation between the backscatter coefficient and the soil moisture was improved after eliminating the vegetation cover. The inversion results of the DBN soil moisture model were further improved through iterative parameters. The model prediction reached its highest level of accuracy when the restricted Boltzmann machine (RBM) was set to seven layers, the bias and R were 0.007 and 0.88, respectively. Ten-fold cross-validation showed that the DBN soil moisture model performed stably with different data. The prediction was further improved when the bare soil backscatter coefficient was used as the training data. The mean values of the root mean square error (RMSE), the inequality coefficient (TIC), and the mean absolute percent error (MAPE) were 0.023, 0.09, and 11.13, respectively.

Research has demonstrated that both family environments and individual characteristics are associated with children's happiness. However, relatively less research has explored whether and how natural environments are associated with children's happiness. The current study examines whether the association between exposure to nature and children's happiness is moderated by temperament (negative affectivity and effortful control), whether there is a gender difference in the moderating mechanisms, and whether the detected moderation supports the diathesis-stress or differential susceptibility models. Four hundred and ten children and one parent of each child participated in our study. We found that boys' effortful control, not negative affectivity, moderated the association between exposure to nature and happiness. Furthermore, the results support the differential susceptibility model with boys' low effortful control as a vulnerability factor. Specifically, for boys with lower effortful control, a lower exposure to nature was associated with lower happiness, and a higher exposure to nature was associated with higher happiness than in boys with higher effortful control. However, girls' negative affectivity and effortful control did not moderate the association between exposure to nature and happiness. These findings suggest that the association between natural environments and children's positive developmental outcomes varies with their effortful control and gender.

Objectives: To assess ultra-early neuroprognostic significance of GFAP, NF-L, UCH-L1, tau, and S100B concentrations, change trajectory, and combination profile after Out-of-Hospital Cardiac Arrest (OHCA). Methods: Prospective enrollment of 22 OHCA and 10 control patients at an academic tertiary care center between May 1, 2017 and January 28, 2020. Blood was collected within one hour of return of spontaneous circulation (ROSC) (H0), at hours 6 (H6), 12, 18, 24, and daily or until discharge or death. Biomarker concentrations, multifactor score, and trajectory change were assessed and compared to final neurologic status (good vs poor Cerebral Performance Category; CPC 1–2 vs CPC 3–5, respectively). Results: 10 patients had good and 12 had poor neurologic outcomes. Poor outcome patients had higher biomarker concentrations and combined biomarker scores at early time points. The earliest significant difference between good and poor outcome patients’ serum biomarkers were at H12 for GFAP (good median: 425 pg/mL [IQR:370−630] vs poor: 5954[1712–65,055] pg/mL; p