Development and validation of a clinical nomogram for predicting in-hospital mortality in patients with traumatic brain injury prehospital: A retrospective study.

Objective: Traumatic brain injury (TBI) is among the leading causes of death and disability globally. Identifying and assessing the risk of in-hospital mortality in traumatic brain injury patients at an early stage is challenging. This study aimed to develop a model for predicting in-hospital mortality in TBI patients using prehospital data from China. Methods: We retrospectively included traumatic brain injury patients who sustained injuries due to external forces and were treated by pre-hospital emergency medical services (EMS) at a tertiary hospital. Data from the pre-hospital emergency database were analyzed, including demographics, trauma mechanisms, comorbidities, vital signs, clinical symptoms, and trauma scores. Eligible patients were randomly divided into a training set (241 cases) and a validation set (104 cases) at a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were employed to identify independent risk factors. Analyzed the discrimination, calibration, and net benefit of the nomogram across both groups. Results: 17.40 % (42/241) of TBI patients died in the hospital in the training set, while 18.30 % (19/104) in the validation set. After analysis, chest trauma (odds ratio [OR] = 4.556, 95 % confidence interval [CI] = 1.861-11.152, P = 0.001), vomiting (OR = 2.944, 95%CI = 1.194-7.258, P = 0.019), systolic blood pressure (OR = 0.939, 95%CI = 0.913-0.966, P < 0.001), SpO2 (OR = 0.778, 95%CI = 0.688-0.881, P < 0.001), and heart rate (OR = 1.046, 95%CI = 1.015-1.078, P = 0.003) were identified as independent risk factors for in-hospital mortality in TBI patients. The nomogram based on the five factors demonstrated well-predictive power, with an area under the curve (AUC) of 0.881 in the training set and 0.866 in the validation set. The calibration curve and decision curve analysis showed that the predictive model exhibited good consistency and covered a wide range of threshold probabilities in both sets. Conclusion: The nomogram based on prehospital data demonstrated well-predictive performance for in-hospital mortality in TBI patients, helping prehospital emergency physicians identify and assess severe TBI patients earlier, thereby improving the efficiency of prehospital emergency care.

Micronuclear battery based on a coalescent energy transducer.

Micronuclear batteries harness energy from the radioactive decay of radioisotopes to generate electricity on a small scale, typically in the nanowatt or microwatt range1,2. Contrary to chemical batteries, the longevity of a micronuclear battery is tied to the half-life of the used radioisotope, enabling operational lifetimes that can span several decades3. Furthermore, the radioactive decay remains unaffected by environmental factors such as temperature, pressure and magnetic fields, making the micronuclear battery an enduring and reliable power source in scenarios in which conventional batteries prove impractical or challenging to replace4. Common radioisotopes of americium (241Am and 243Am) are α-decay emitters with half-lives longer than hundreds of years. Severe self-adsorption in traditional architectures of micronuclear batteries impedes high-efficiency α-decay energy conversion, making the development of α-radioisotope micronuclear batteries challenging5,6. Here we propose a micronuclear battery architecture that includes a coalescent energy transducer by incorporating 243Am into a luminescent lanthanide coordination polymer. This couples radioisotopes with energy transducers at the molecular level, resulting in an 8,000-fold enhancement in energy conversion efficiency from α decay energy to sustained autoluminescence compared with that of conventional architectures. When implemented in conjunction with a photovoltaic cell that translates autoluminescence into electricity, a new type of radiophotovoltaic micronuclear battery with a total power conversion efficiency of 0.889% and a power per activity of 139 microwatts per curie (µW Ci-1) is obtained.

Comparison of the surgical efficacy of robot-assisted and freehand nail placement in the treatment of sarcopenia combined with femoral neck fractures younger than 65 years.

OBJECTIVE: There is limited research on the effectiveness of orthopedic robot-assisted treatment for sarcopenia combined with femoral neck fractures (FNF) in clinical settings. This study aimed to compare the clinical outcomes of orthopedic robot-assisted screw placement with traditional manual screw placement for treating sarcopenia combined with FNF. METHODS: The retrospective study included patients with FNF under the age of 65 who were admitted to the Department of Orthopedics at XX Hospital Affiliated to XX University between January 2019 and March 2022 and underwent internal fixation with cannulated screws. Grip strength of the dominant hand was measured, and the skeletal muscle index (SMI) was calculated based on the muscle tissue area at the level of the 12th thoracic vertebrae on chest CT divided by height squared. Sarcopenia was diagnosed when SMI was below 42.6 cm2/m2 for men or 30.6 cm2/m2 for women. Patients were then grouped based on whether they underwent orthopedic robot-assisted surgery, as the robot-assisted (RA) group or the freehand (FH) group. Follow-up evaluations over 24-36 months included various parameters such as operation time, blood loss, X-ray shots, number of needle drilling, cannulated nail parallelism, C-reactive protein (CRP) levels, time to weight-bearing, perioperative infection, VAS (visual analogue scale) scores at 1 and 6 months post-surgery, Harris hip score at 6 months post-surgery, and incidence of nonunions and femoral head necrosis within 24 months post-surgery. RESULTS: A total of 127 participants were enrolled in this study, with 46 individuals in the RG group and 81 in the FG group. Across both groups, factors such as gender, age, SMI, injury sides, Garden classifications, intraoperative blood loss, preoperative CRP, and VAS scores at 6 months post-surgery did not show statistically significant differences (p > 0.05). The RA group exhibited shorter operation time, fewer intraoperative X-ray shots, less needle drilling, and lower postoperative CRP levels compared to the FH group. The VAS score of the RA group was lower one month after surgery, whereas the Harris score was higher six months post-surgery (p < 0.05). The parallel angle of the hollow screws in the RA group was superior to that in the FH screw placement group, with an earlier time to bear weight on the ground post-surgery (p < 0.05). There were no statistically significant differences in incision infection, femoral neck nonunion (within 9 months after surgery), and patient satisfaction between the two groups (p > 0.05). Furthermore, the rate of femoral head necrosis after fracture within 2 years in the RA group was lower compared to the FH screw placement group, with statistically significant differences (p < 0.05).

Effectiveness of Lanzhou Lamb Rotavirus Vaccine and RotaTeq Against Hospitalized Rotavirus Infections Among Children During 2020-2023 in Guangdong Province, China: A Test-Negative Case-Control Study.

INTRODUCTION: The evidence regarding the effectiveness of Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5) against gastroenteritis (RVGE) caused by emerging genotypes in Chinese children remains limited. METHODS: We conducted a test-negative case-control study using gastroenteritis surveillance data from four cities (2020-2023) in Guangdong Province, China. Children aged 2 months to 5 years hospitalized with acute gastroenteritis were enrolled. Cases were rotavirus-positive; controls were rotavirus-negative. Vaccine effectiveness (VE) was estimated using multivariable logistic regressions. RESULTS: Among 2650 children, 218 (8.2%) were rotavirus-positive, predominantly G8P[8]. Also, 1543 (58.23%) children were unvaccinated, while 632 (23.85%) and 475 (17.92%) received at least one dose of RV5 and LLR, respectively. Adjusted RV5 VE against any RVGE severity was 51.7% [95% confidence interval (CI) - 58.1-85.3%]) for one dose, 37.6% (95% CI - 58.5-75.4%) for two doses, and 64.1% (95% CI 38.0-79.2%) for three doses. For LLR, VE against any RVGE severity was 38.7% (95% CI 5.7-60.2%) for one dose, 74.6% (95% CI 35.3-90.0%) for two doses, and 58.8% (95% CI - 217.6-94.6%) for three doses. Against severe RVGE, RV5 VE was 67.2% (95% CI - 144.7-95.6%) for one dose, 74.0% (95% CI - 92.1-96.5%) for two doses, and 86.6% (95% CI 56.8-95.9%) for three doses. For LLR, VE against severe RVGE was 57.7% (95% CI 20.3-77.6%) for one dose, 73.4% (95% CI 11.9-92.0%) for two doses, and - 27.8% (95% CI - 949.7-84.4%) for three doses. CONCLUSIONS: Both RV5 and LLR provided protection against RVGE, including the emerging G8P[8] genotype. Three doses of RV5 offered strong protection, while two doses of LLR also appeared to be an effective strategy against rotavirus infection.

Rotavirus is a common cause of severe diarrhea in young children, and vaccines are crucial in preventing this illness. This study looked at how well two rotavirus vaccines, Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5), protect children against rotavirus gastroenteritis (RVGE), including infections caused by a new strain called G8P[8]. We analyzed data from children aged 2 months to 5 years who were hospitalized between 2020 and 2023. We compared children who tested positive for rotavirus (cases) with those who tested negative (controls) to determine how well the vaccines worked. Our results showed that both RV5 and LLR vaccines provided protection against RVGE. For RV5, three doses provided strong protection, while for LLR, two doses provided good protection. Against severe RVGE, three doses of RV5 were effective, while two doses of LLR also showed good protection.

Highly selective removal of thallous ions from wastewater using Prussian Blue biochar composite.

Thallium, a highly toxic pollutant, shows greater toxicity to human than other common heavy metals such as mercury, lead, cadmium and its effective removal from wastewater gains great attention. The main restriction for the Tl+ removal is the interference of a high concentration of co-existing ions in wastewater. Therefore, the goal of the current work was to synthesis adsorbent with high selectivity for the Tl+ removal. Herein, the pore size sieving strategy was proposed and Prussian blue-impregnated biochar (BC@PB) particles was synthesized. More than 95% Tl+ can be removed even the concentrations of the coexistence ions (Na+, Cd2+, and Zn2+) 1,000 higher than the initial concentration of Tl+ (500 µg/L). BC@PB also showed large adsorption capacity (9365 µg/g) and more than 99% Tl+ (initial concentration, 500 µg/L) were removed in just 1 min. The BC@PB had excellent and stable Tl+ removal ability (> 99%) over a range of pH from 3 to 9, which covered the pH range of common thallium-containing wastewater. The density functional theory (DFT) calculation confirmed that not only hydrated volume but also the hydration free energy of ions, which governed the energy barrier for ions entering into narrow channels of BC@PB, played essential roles on the selectivity removal of Tl+. Overall, due to its high selectivity, high adsorption capacity and easy preparation process, the synthesized BC@PB particles based on the pore sizing sieving strategy, can be a promising candidate for the removal of thallium from wastewater.

Gastrointestinal bleeding caused by splenic artery pseudoaneurysm in chronic pancreatitis: a case report and literature review.

Pseudoaneurysm of the splenic artery is a rare vascular complication of chronic pancreatitis, with a high mortality rate. Haemorrhage and abdominal pain are the most common manifestations, and so far there are no literature reviews on the rare complication of splenic artery pseudoaneurysm due to chronic pancreatitis. Therefore, we describe a male patient with worsening haemochezia and upper abdominal pain, who had been hospitalized repeatedly for 'pancreatitis' 1 year ago, and relevant investigations confirmed a pseudoaneurysm of the splenic artery, which was successfully treated by transarterial embolization, and a literature review is also presented.

Lauric acid improved the quality of fresh noodles with/without sodium bicarbonate by altering physical properties and structure of wheat starch.

To know the influence of lauric acid (LA) on wheat flour fresh noodles (WFN) quality and the latent mechanism, the effect of LA on cooking properties, digestibility and structure of WFN with/without sodium bicarbonate (SB) and the properties of wheat flour (WF) with/without SB were studied. The results indicated that LA reduced cooking loss and digestibility of WFN with SB and slightly decreased water adsorption and increased the free water binding ability and hardness of WFN without SB. Furthermore, LA increased the degree of short- and long-range order and molecular weight of starch in cooked WFN with/without SB and it had greater effect on the degree of short- and long-range order and molecular weight of starch in cooked WFN with SB than that without SB. Differential scanning calorimeter (DSC) and rapid viscosity analysis (RVA) displayed that WFN with LA and SB formed more starch-LA or/and starch-LA-protein complexes than WFN with LA. Additionally, the impact of LA on WFN quality and WF properties was influenced by SB concentration. This study will provide theoretical basis and new thoughts for the design of high-quality fresh noodles with low digestibility, low cooking loss and high hardness.

Direct Access to 3,4,6-Trisubstituted 2-Pyrones via Carbene Catalysis.

An N-heterocyclic carbene-catalyzed [4 + 2] annulation of ß,γ-unsaturated α-keto esters and phenylacetate esters was developed for the direct and efficient construction of 2-pyrones. This approach provides a practical synthesis pathway for various 3,4,6-trisubstituted 2-pyrones in moderate to good yields and features broad substrate scope and good functional group tolerance. Moreover, the products can also be readily transformed to naphthalene and acylamide.

Experimental study of rock fracture behavior under direct tension using three-dimensional digital image correlation.

Understanding the mechanical characteristics of rocks when subjected to direct tension is crucial for assessing the stability of rock formations. Within the scope of this research, a series of tests was conducted using Tage tuff to assess the deformation behavior and crack extension of rock under direct tension. The axial, lateral, and shear strain fields as well as crack propagation, localized deformation behavior, and failure mode of the rocks were analyzed using three-dimensional digital image correlation method. The results showed that the axial strain fields on the specimen surface were heterogeneous, with different locations and localization occurring in the pre-peak stage, which was similar to the evolution of shear strain, whereas the lateral strain only showed slight changes. The crack extension direction was inferred, indicating that both tensile and shear stress occurred in the tests. Furthermore, different stress-strain responses were observed for the inside and outside of the localized bands. Then, the surface patterns of specimen failure were scanned and analyzed to assess the failure mode and residual strength of the specimen under direct tensile stress. Finally, the results of direct tension, uniaxial compression, and Brazilian split tests for Tage tuff were compared, and the complete stress-strain curve of uniaxial tension (UT) was simulated using a nonlinear-variable-compliance constitutive equation. This study provides a deeper understanding into the damage behavior of rocks under direct tension.

Metformin relieves bone cancer pain by reducing TGFßRI-TRPV1 signaling in rats.

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFß1 in the metastatic bone tissue, and raised the expression of TGFßRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFßRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFß1, TGFßRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFß1-TGFßRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

Does Tranexamic Acid Reduce Elbow Swelling and Improve Early Function Following Arthroscopic Arthrolysis? A Double-Blind Randomized Controlled Trial.

BACKGROUND: Tranexamic acid (TXA) reduces bleeding and hematoma rates in open elbow arthrolysis. However, its effects on arthroscopic elbow arthrolysis remain unclear. This study aims to evaluate the effect of TXA on elbow arthroscopic procedures and compare bleeding volume, hemarthrosis, visual analog scale (VAS) for pain, range of motion (ROM), and Mayo Elbow Performance Score (MEPS) in the early postoperative period between patients who received intra-articular TXA and those who did not. METHODS: A prospective, double-blind, randomized controlled trial enrolling 80 patients with stiff elbows who underwent arthroscopic arthrolysis was performed from January 2021 to December 2022. Intra-articularly, 1 g of TXA in 100 ml of saline or placebo (control group) was administered after the arthroscopic operation according to randomization. Parameters were recorded and compared between the groups, including bleeding volume of drainage, hemoglobin (Hgb) level, ratio of arm and forearm circumference of the surgical side to the contralateral side, grading of hematoma, VAS, ROM and MEPS within one week postoperatively. And during one year follow-up, ROM and MEPS were recorded. RESULTS: All patients enrolled in this study demonstrated significant improvements in ROM (flexion-extension) and MEPS one week postoperatively, with no significant differences observed between the two groups. Compared to the control group, the TXA group exhibited significant differences in the bleeding volume of drainage (61.45±47.7 ml vs. 89.8±47.0 ml, p=0.030) and a higher Hgb level 24 hours postoperatively (13.5±1.5 g/dL vs. 12.6±1.8 g/dL p=0.049). While the ratio of arm and forearm circumferences significantly increased 24 hours postoperatively compared to preoperative values in TXA group (1.05±0.06 vs. 1.02±0.04 and 1.02±0.06 vs. 0.98±0.04, with p=0.019 and p=0.005, respectively), this difference vanished one week postoperatively for the ratio of arm circumference. However, it persisted for the ratio of forearm circumference (1.02±0.07 vs. 0.98±0.04, p=0.003). Furthermore, there was no significant difference in MEPS, VAS or ROM between the two groups one week postoperatively. CONCLUSION: Patients with stiff elbows who underwent arthroscopic arthrolysis achieved satisfactory clinical outcomes very early postoperatively. Compared to the control group, patients who underwent arthroscopic elbow arthrolysis with intra-articular administration of TXA exhibited significantly less bleeding volume of drainage and slightly higher Hgb levels postoperatively. One week postoperatively, slightly more swelling in the upper arm region was noted in the control group compared to the TXA group. These findings suggest that the intra-articular injection of TXA after arthroscopic release for elbow stiffness may statistically reduce complications related to postoperative bleeding. However, it's clinical relevance needs further investigation.

[Comparative study of short-term effectiveness of three surgical methods for ulnar styloid base fracture complicated with triangular fibrocartilage complex injury].

Objective: To compare the short-term effectiveness of arthroscopic suture of triangular fibrocartilage complex (TFCC), arthroscopic suture of TFCC combined with open reduction and internal fixation, and simple open reduction and internal fixation in the treatment of distal radius fractures combined with ulnar styloid base fractures and TFCC injury. Methods: A clinical data of 97 patients with distal radius fractures combined with ulnar styloid base fracture and TFCC injury, who were admitted between September 2019 and September 2022 and met the selective criteria, was retrospectively analyzed. After reduction and internal fixation of distal radius fractures, 37 cases underwent arthroscopic suture of TFCC (TFCC group), 31 cases underwent arthroscopic suture of TFCC combined with open reduction and internal fixation of ulnar styloid base fractures (combination group), and 29 cases underwent simple open reduction and internal fixation of ulnar styloid base fractures (internal fixation group). There was no significant difference in baseline data between groups ( P>0.05), such as gender, age, injury side, time from injury to operation, and preoperative radius height, palm inclination, ulnar deviation, grip strength, wrist range of motion (ROM) in rotation, ulnar-radial deviation, and flexion-extension. The differences (change value) in radius height, metacarpal inclination angle, ulnar deviation angle, grip strength, and wrist ROM in rotation, ulnar-radial deviation, and flexion-extension between preoperative and 12 months after operation in 3 groups were compared. The effectiveness was evaluated according to the modified Gartland-Werley score at 12 months after operation. Results: All incisions healed by first intention. All patients were followed up 12-18 months (mean, 14 months). X-ray films showed that there were 4 patients with non-union of ulnar styloid base fracture in TFCC group, and the remaining patients had fracture healing at 3 months after operation. The radius height, palm inclination, and ulnar deviation of 3 groups at 12 months after operation were significantly better than those before operation ( P<0.05); however, the differences in the change values of the above indexes between groups was not significant ( P>0.05). At 12 months after operation, the change values of wrist ROM in rotation, ulnar-radial deviation, and flexion-extension in the TFCC group and the combination group were significantly greater than those in the internal fixation group ( P<0.05), and there was no significant difference between the TFCC group and the combination group ( P>0.05). The change values of grip strength was significantly greater in the combination group than in the internal fixation group ( P<0.05); there was no significant difference between the other groups ( P>0.05). The excellent and good rates according to the modified Gartland-Werley score were 91.89% (34/37), 93.54% (29/31), and 72.41% (21/29) in the TFCC group, the combination group, and the internal fixation group, respectively. The excellent and good rates of the TFCC group and the combination group were significantly higher than that of the internal fixation group ( P<0.05); there was no significant difference between the TFCC group and the combination group ( P>0.05). Conclusion: For ulnar styloid base fractures with TFCC injury, compared with simple open reduction and internal fixation, arthroscopic suture of TFCC or suture TFCC combined with internal fixation treatment are both beneficial for wrist function recovery, and their short-term effectiveness are similar. Therefore, arthroscopic suture of TFCC may be a better choice.

Nationwide meta-analysis of microplastic distribution and risk assessment in China's aquatic ecosystems, soils, and sediments.

Microplastic (MP) accumulation has recently become a pressing global environmental challenge. As a major producer and consumer of plastic products, China's MP pollution has garnered significant attention from researchers. However, accurate and comprehensive investigations of national-level MP pollution are still lacking. In this study, we systematically collated a national MP pollution dataset consisting of 7766 water, soil, and sediment sampling sites from 544 publicly published studies, revealing the spatiotemporal distribution and potential risks of MP pollution in China. The results indicate that MP distribution is influenced by various regional factors, including economic development level, population distribution, and geographical environment, exhibiting considerable range and complexity. MP concentrations are generally higher in economically prosperous areas, but the degree of pollution varies significantly across different environmental media. Given the uncertainty and lack of standardized data in traditional microplastic risk assessment methods, this article highlights the urgency of developing a comprehensive big data and artificial intelligence (AI)-based regulatory framework. This work provides a substantial amount of accurate MP pollution data and offers a fresh perspective on leveraging AI for microplastic pollution regulation.

In vivo detection of the epimer metabolites of sweroside via ultra-performance liquid chromatography time-of-flight mass spectrometry combined with DNPH derivatization.

The metabolites of sweroside were first investigated in vivo with ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) in combination with 2,4-dinitrophenylhydrazine derivatization. In addition, the mass detection sensitivity of the major metabolites, epinaucledal and naucledal, via UPLC-TOF-MS was significantly enhanced, and the epimer metabolites were distinctly discovered from plasma following gavage of sweroside in rats. The plasma concentration of epinaucledal and naucledal was quantified via UPLC-TOF-MS in negative mode using erythrocentaurin as the internal standard. The maximum mean plasma concentrations of naucledal and epinaucledal were 75.36 ± 20.10 and 43.52 ± 15.60 ng/ml within 2 h, respectively, following gavage of sweroside at 20 mg/kg. Moreover, the area under the concentration-time curve of naucledal was three times that of epinaucledal. The metabolic process of conversion of sweroside to epinaucledal and naucledal was deduced, and the pharmacological effects of epinaucledal and naucledal will clarify the clinical efficacy of sweroside.

Real biofuel and fossil-fuel soot combustion activities in active and passive regeneration of diesel/gasoline particulate filters under different O2/NOx concentrations.

In this work, we aim to investigate and compare the combustion reactivities of real biofuel soot and fossil-fuel soot in the active and passive regeneration conditions of DPF and GPF through temperature-programmed oxidation (TPO). Higher reactivity of biofuel soot is achieved even under GPF conditions with extremely low oxygen concentration (~ 1%), which provides a great potential for low-temperature regeneration of GPF. Such a result is mainly attributed to the low graphitization and less surface C = C groups of biofuel soot. Unfortunately, the presence of high-content ashes (~ 47%) and P impurity in real biofuel soot hinder its combustion reactivity. TPO evidences that the O2/NOX-lacking conditions in GPF are key factors to impact the combustion of soot, especially fossil-fuel soot. This work provides some useful information for understanding real biofuel and fossil-fuel soot combustion in GPF and DPF regeneration and further improvement in filter regeneration process.

Molecular engineering of a theranostic molecule that detects Aß plaques, inhibits Iowa and Dutch mutation Aß self-aggregation and promotes lysosomal biogenesis for Alzheimer's disease.

Extracellular clustering of amyloid-ß (Aß) and an impaired autophagy lysosomal pathway (ALP) are the hallmark features in the early stages of incurable Alzheimer's disease (AD). There is a pressing need to find or develop new small molecules for diagnostics and therapeutics for the early stages of AD. Herein, we report a small molecule, namely F-SLCOOH, which can bind and detect Aß1-42, Iowa mutation Aß, Dutch mutation Aß fibrils and oligomers exhibiting enhanced emission with high affinity. Importantly, F-SLCOOH can readily pass through the blood-brain barrier and shows highly selective binding toward the extracellular Aß aggregates in real-time in live animal imaging of a 5XFAD mice model. In addition, a high concentration of F-SLCOOH in both brain and plasma of wildtype mice after intraperitoneal administration was found. The ex vivo confocal imaging of hippocampal brain slices indicated excellent colocalization of F-SLCOOH with Aß positive NU1, 4G8, 6E10 A11 antibodies and THS staining dye, affirming its excellent Aß specificity and targetability. The molecular docking studies have provided insight into the unique and specific binding of F-SLCOOH with various Aß species. Importantly, F-SLCOOH exhibits remarkable anti-fibrillation properties against toxic Aß aggregate formation of Aß1-42, Iowa mutation Aß, and Dutch mutation Aß. F-SLCOOH treatment also exerts high neuroprotective functions and promotes autophagy lysosomal biogenesis in neuronal AD cell models. In summary, the present results suggest that F-SLCOOH is a highly promising theranostic agent for diagnosis and therapeutics of AD.

Thorium Cluster Synthesized by a Solvent-Free Flux Approach: The Richest Coordination Diversity and Application Exploration.

The renaissance of research interests in actinide oxo clusters in the past decade arises from both the concerns of radioactive contamination and their potential utility as nanoscale materials. Compared to the uranium cluster, the thorium (Th) cluster shows less coordination variation. Herein, we presented a unique Th cluster (ThC-1) that exhibits the most diverse coordination chemistry found within a single Th cluster via a solvent-free flux synthesis approach. The melt triazole not only offers a unique solvation environment that may be responsible for the coordination diversity in ThC-1 but also represents the first nitrogen-donor capping ligand in Th clusters. The potential utility of ThC-1 as a heterogeneous catalyst was also explored for a classical CO2 cycloaddition reaction. This work offers a novel approach in synthesizing Th clusters, broadening the realm of the structural diversity of Th.

Spautin-1 promotes PINK1-PRKN-dependent mitophagy and improves associative learning capability in an alzheimer disease animal model.

Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 and promoting the degradation of the PIK3C3/VPS34-BECN1 complex, while its effect on selective autophagy remains poorly understood. Mitophagy is a selective form of autophagy for removal of damaged and superfluous mitochondria via the autophagy-lysosome pathway. Here, we report a surprising discovery that, while spautin-1 remains as an effective autophagy inhibitor, it promotes PINK1-PRKN-dependent mitophagy induced by mitochondrial damage agents. Mechanistically, spautin-1 facilitates the stabilization and activation of the full-length PINK1 at the outer mitochondrial membrane (OMM) via binding to components of the TOMM complex (TOMM70 and TOMM20), leading to the disruption of the mitochondrial import of PINK1 and prevention of PARL-mediated PINK1 cleavage. Moreover, spautin-1 induces neuronal mitophagy in Caenorhabditis elegans (C. elegans) in a PINK-1-PDR-1-dependent manner. Functionally, spautin-1 is capable of improving associative learning capability in an Alzheimer disease (AD) C. elegans model. In summary, we report a novel function of spautin-1 in promoting mitophagy via the PINK1-PRKN pathway. As deficiency of mitophagy is closely implicated in the pathogenesis of neurodegenerative disorders, the pro-mitophagy function of spautin-1 might suggest its therapeutic potential in neurodegenerative disorders such as AD.Abbreviations: AD, Alzheimer disease; ATG, autophagy related; BafA1, bafilomycin A1; CALCOCO2/NDP52, calcium binding and coiled-coil domain 2; CCCP, carbonyl cyanide m-chlorophenyl hydrazone; COX4/COX IV, cytochrome c oxidase subunit 4; EBSS, Earle's balanced salt; ECAR, extracellular acidification rate; GFP, green fluorescent protein; IA, isoamyl alcohol; IMM, inner mitochondrial membrane; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MMP, mitochondrial membrane potential; mtDNA, mitochondrial DNA; nDNA, nuclear DNA; O/A, oligomycin-antimycin; OCR, oxygen consumption rate; OMM, outer mitochondrial membrane; OPTN, optineurin; PARL, presenilin associated rhomboid like; PINK1, PTEN induced kinase 1; PRKN, parkin RBR E3 ubiquitin protein ligase; p-Ser65-Ub, phosphorylation of Ub at Ser65; TIMM23, translocase of inner mitochondrial membrane 23; TOMM, translocase of outer mitochondrial membrane; USP10, ubiquitin specific peptidase 10; USP13, ubiquitin specific peptidase 13; VAL, valinomycin; YFP, yellow fluorescent protein.

The viral trends and genotype diversity of norovirus in the wastewater of Shenzhen, China.

Norovirus (NoV) is the primary cause of acute gastroenteritis (AGE) on a global scale. Numerous studies have demonstrated the immense potential of wastewater surveillance in monitoring the prevalence and spread of NoV within communities. This study employed a one-step reverse transcription-quantitative PCR to quantify NoV GI/GII in wastewater samples (n = 2574), which were collected once or twice a week from 38 wastewater treatment plants from March 2023 to February 2024 in Shenzhen. The concentrations of NoV GI and GII ranged from 5.0 × 104 to 1.7 × 106 copies/L and 4.1 × 105 to 4.5 × 106 copies/L, respectively. The concentrations of NoV GII were higher than those of NoV GI. Spearman's correlation analysis revealed a moderate correlation between the concentration of NoV in wastewater and the detection rates of NoV infections in sentinel hospitals. Baseline values were established for NoV concentrations in Shenzhen's wastewater, providing a crucial reference point for implementing early warning systems and nonpharmaceutical interventions to mitigate the impact of potential outbreaks. A total of 24 NoV genotypes were identified in 100 wastewater samples by sequencing. Nine genotypes of NoV GI were detected, with the major genotypes being GI.4 (38.6 %) and GI.3 (21.8 %); Fifteen genotypes of NoV GII were identified, with GII.4 (53.6 %) and GII.17 (26.0 %) being dominant. The trends in the relative abundance of NoV GI/GII were significantly different, and the trends in the relative abundance of NoV GII.4 over time were similar across all districts, suggesting a potential risk of cross-regional spread. Our findings underscore the effectiveness of wastewater surveillance in reflecting population-level NoV infections, capturing the diverse array of NoV genotypes, and utilizing NoV RNA in wastewater as a specific indicator to supplement clinical surveillance data, ultimately enhancing our ability to predict the timing and intensity of NoV epidemics.

Regio- and Diastereoselective Synthesis of Polysubstituted Piperidines Enabled by Boronyl Radical-Catalyzed (4+2) Cycloaddition.

Piperidines are widely present in small molecule drugs and natural products. Despite many methods have been developed for their synthesis, new approaches to polysubstituted piperidines are highly desirable. This work presents a radical (4+2) cycloaddition reaction for synthesis of piperidines featuring dense substituents at 3,4,5-positions that are not readily accessible by known methods. Using commercially available diboron(4) compounds and 4-phenylpyridine as the catalyst precursors, the boronyl radical-catalyzed cycloaddition between 3-aroyl azetidines and various alkenes, including previously unreactive 1,2-di-, tri-, and tetrasubstituted alkenes, has delivered the polysubstituted piperidines in generally high yield and diastereoselectivity. The reaction also features high modularity, atom economy, broad substrate scope, metal-free conditions, simple catalysts and operation. The utilization of the products has been demonstrated by selective transformations. A plausible mechanism, with the ring-opening of azetidine as the rate-limiting step, has been proposed based on the experimental and computational results.