Covalent adaptable polymer networks with CO2-facilitated recyclability.

Cross-linked polymers with covalent adaptable networks (CANs) can be reprocessed under external stimuli owing to the exchangeability of dynamic covalent bonds. Optimization of reprocessing conditions is critical since increasing the reprocessing temperature costs more energy and even deteriorates the materials, while reducing the reprocessing temperature via molecular design usually narrows the service temperature range. Exploiting CO2 gas as an external trigger for lowering the reprocessing barrier shows great promise in low sample contamination and environmental friendliness. Herein, we develop a type of CANs incorporated with ionic clusters that achieve CO2-facilitated recyclability without sacrificing performance. The presence of CO2 can facilitate the rearrangement of ionic clusters, thus promoting the exchange of dynamic bonds. The effective stress relaxation and network rearrangement enable the system with rapid recycling under CO2 while retaining excellent mechanical performance in working conditions. This work opens avenues to design recyclable polymer materials with tunable dynamics and responsive recyclability.

The peptide-based bispecific CAR T cells target EGFR and tumor stroma for effective cancer therapy.

BACKGROUND AND PURPOSE: The efficacy of chimeric antigen receptor (CAR)-T cell for solid tumors is limited partially because of the lack of tumor-specific antigens and off-target effects. Low molecular weight peptides allowed CAR T cell to display several antigen receptors to reduce off-target effects. Here, we develop a peptide-based bispecific CAR for EGFR and tumor stroma, which are expressed in a variety of tumor types. EXPERIMENTAL APPROACH AND KEY RESULTS: The peptide-based CAR T cells show excellent proliferation, cytotoxicity activity and are only activated by tumor cells overexpressing EGFR instead of normal cells with low EGFR expressing. In mouse xenograft models, the peptide bispecific CAR T cells can be delivered into the inner of tumor masses and thus are effective in inhibiting tumor growth. Meanwhile, they show strong expansion capacity and the property of maintaining long-term function in vivo. During treatment, no off-tumor toxicity is observed on healthy organs expressing lower levels of EGFR. CONCLUSIONS & IMPLICATIONS: Our findings demonstrate that peptide-based bispecific CAR T holds great potential in solid tumor therapy due to an excellent targeting ability towards tumors and tumor microenvironment.

Multimodal imaging for the differential diagnosis and efficacy evaluation of intraocular retinoblastoma in children with selective ophthalmic artery infusion.

Background: Retinoblastoma (RB) is the most common malignant tumor in children under the age of 3 years and is associated with a high disability and mortality rate. The aim of this study was, first, to evaluate the clinical efficacy of multimodal imaging in differentially diagnosing RB in children and in predicting the efficacy of selective ophthalmic artery infusion (SOAI) and, second, to identify the factors associated with this efficacy. Methods: This study retrospectively collected the data from 256 children with unilateral RB and intraocular involvement, including multimodal imaging magnetic resonance imaging (MRI), computed tomography (CT), and clinical characteristics. Among the cases, 33 with both CT and MRI data available were used to evaluate the diagnostic accuracy in distinguishing RB, with histopathological results serving as the gold standard. Additionally, a retrospective analysis was conducted on the MRI and clinical characteristics of 256 cases of unilateral RB with intraocular involvement before SOAI treatment. The predictive ability of imaging features and clinical characteristics for the treatment efficacy of children was analyzed, and the differences in globe salvage rates and visual preservation based on different tumor stages were evaluated. Results: The diagnostic accuracy of CT imaging for RB was 96.96% while that of MRI was 84.84%, with both showing high consistency with the histopathological results. CT images demonstrated a posterior intraocular mass with a high-density appearance, with spots, patches, or clustered calcifications visible within the tumor. The CT values were mostly above 100 Hounsfield units (HU), and enhanced scanning showed varying degrees of enhancement in noncalcified masses. MRI showed low or moderate signal intensity on T1-weighted images and moderate-to-high signal intensity on T2-weighted images, with significant enhancement after contrast administration. Tumors with more calcifications showed long T1 and short T2 signals. Patients with better prognosis had a higher delta signal increase (ΔSI), a greater distance from the optic disc, smaller tumor diameter, absence of implantation nodules or smaller implantation range, endogenous growth pattern, smaller extent of retinal detachment, absence of clinical high-risk factors, no vitreous hemorrhage, no globe shrinkage, and smaller calcification volume. The distance between the tumor and optic disc, clinical high-risk factors, and tumor growth pattern were found to be independent factors associated with prognosis. The rate of successful globe salvage and visual acuity decreased with increasing tumor stage. Conclusions: CT and MRI are highly valuable for the comprehensive assessment of tumors in pediatric RB. MRI alone can complete a comprehensive assessment of patients with RB and thus allow for the reduction radiation dose in children. Calcification of the tumor is crucial for diagnosis, and imaging findings can serve to inform patient prognosis and treatment planning. The distance between the tumor and optic disc, clinical high-risk factors, and tumor growth pattern are closely related to the prognosis of children.

Manipulation of Exchange Bias in Two-Dimensional van der Waals Ferromagnet Near Room Temperature.

As a host for exchange bias (EB), van der Waals (vdW) magnetic materials have exhibited intriguing and distinct functionalities from conventional magnetic materials. The EB in most vdW systems is far below room temperature, which poses a challenge for practical applications. Here, by using Kerr microscopy, we demonstrate a record-high blocking temperature that approaches room temperature and a huge positive EB field that nears 2 kOe at 100 K in naturally oxidized two-dimensional (2D) vdW ferromagnetic Fe3GaTe2 nanoflakes. Moreover, we realized a reversible manipulation of both the presence/absence and positive/negative signs of EB via a training magnetic field without multiple field cooling processes. Thus, our study clearly reveals the robust, sizable, and sign-tunable EB in vdW magnetic materials up to near room temperature, thereby establishing Fe3GaTe2 as an emerging room-temperature-operating vdW material and paving the way for designing practical 2D spintronic devices.

Comparison Study Among Three Surgical Methods in the Treatment of Isolated Fractures of the Greater Tuberosity of the Humerus.

Introduction: This study aimed to compare the efficacy of three methods for isolated greater tuberosity fractures of the humerus. Methods: A retrospective review of patients with isolated humeral greater tuberosity fractures between January 2013 and June 2021 in our institution. We recorded data on patient demographics, injury characteristics, preoperative and postoperative imaging findings, length of incision, operative time, and intraoperative blood loss. Results: A total of 107 patients met the inclusion criteria and were divided into three groups. 50 patients in group A were administered a proximal humeral internal locking system (PHILOS) plate fixed using the deltopectoral approach, 26 patients in group B were administered a PHILOS plate fixed using the deltoid-splitting approach, and 31 patients in group C were administered a novel anatomical plate fixed using the deltoid-splitting approach. No significant differences were identified in sex, age, injury mechanism, type of fracture, dominant side limb, or shoulder anterior joint dislocation. However, the operative time, blood loss, and the length of incision was shorter than in Group C. Moreover, pain was evaluated on the third and fifth days after surgery; pain was lower in Group C, and pain at the last follow-up was not different between the groups. No significant differences were identified in the Constant score, DASH score, and ROM at the last follow-up. 2 patients were diagnosed with subacromial impingement, 1 in Group A one in Group B, and 1 patient in Group B experienced axillary nerve injury after surgery. Conclusion: The novel anatomical plate fixed using the deltoid-splitting approach can achieve good results in the treatment of isolated humeral greater tubercle fractures with less blood loss, shorter operative time, and shorter surgical incisions, and can relieve pain in the early postoperative period.

Influencing factors for pediatric eye disorders and health related quality of life: a cross-sectional study in Shanghai, China.

Background: Myopia, strabismus, and ptosis are common pediatric eye diseases, which have a negative impact on children and adolescents in terms of visual function, mental health, and health-related quality of life (HRQoL). Therefore, this study focused on those pediatric eye diseases by analyzing their risk factors and HRQoL for the comprehensive management of myopia, strabismus, and ptosis. Methods: A total of 363 participants (2-18 years old) were included in this study for risk factors analysis of myopia, strabismus, and ptosis. We collected demographic characteristics, lifestyle habits and eye care habits of these children and analyzed them by using univariable and multivariable logistic regression. In addition, we applied the Chinese version of Pediatric Quality of Life Inventory-Version 4.0 (PedsQL 4.0) to assess HRQoL in 256 children with strabismus and ptosis. Univariable and multivariable linear regression models were applied to evaluate potential influencing factors of HRQoL. Results: Of all the participants, 140 had myopia, 127 had strabismus, and 145 had ptosis. Based on the multivariable logistic regression analysis model, we found that the history of parental myopia and daily average near-distance eye usage time were risk factors for myopia, and increased body mass index (BMI) was identified as a risk factor for strabismus and ptosis. Individuals with ptosis possessed decreased HRQoL. The multivariable linear regression model suggested that daily average near-distance eye usage time, light intensity during visual tasks, and daily average sleep duration had potential influences on HRQoL. Conclusion: This is the first study to assess the risk factors and HRQoL of myopia, strabismus, and ptosis together. We identified risk factors for these common pediatric eye diseases to help doctors, parents, and teachers better manage them. Our study discovered that children with eye disorders exhibit a notably diminished HRQoL. Consequently, it emphasizes the necessity for increased social attention and mental health assistance for these children.

Unlocking the potential: advancements and future horizons in ROR1-targeted cancer therapies.

While receptor tyrosine kinase-like orphan receptor 1 (ROR1) is typically expressed at low levels or absent in normal tissues, its expression is notably elevated in various malignant tumors and conditions, including chronic lymphocytic leukemia (CLL), breast cancer, ovarian cancer, melanoma, and lung adenocarcinoma. This distinctive feature positions ROR1 as an attractive target for tumor-specific treatments. Currently, several targeted drugs directed at ROR1 are undergoing clinical development, including monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor T-cell therapy (CAR-T). Additionally, there are four small molecule inhibitors designed to bind to ROR1, presenting promising avenues for the development of PROTAC degraders targeting ROR1. This review offers updated insights into ROR1's structural and functional characteristics, embryonic development implications, cell survival signaling pathways, and evolutionary targeting strategies, all of which have the potential to advance the treatment of malignant tumors.

A versatile fluorescent probe for the ratiometric detection of hydrazine (N2H4) in water, soil, plant, and food samples.

Hydrazine (N2H4) is a crucial chemical raw material extensively utilized in chemical production. However, due to its volatility, water solubility, and high toxicity, both the gaseous form and aqueous solution of N2H4 pose significant environmental risks by causing severe pollution that can adversely impact plants, microorganisms, and human health. Therefore, accurate detection of N2H4 in the environment is imperative for safeguarding public health. In this study, we synthesized a ratiometric fluorescent probe (BCaz-Cy2) based on Carbazole and Hemicyanine groups. This probe exhibits simple synthesis procedure, rapid response time, high sensitivity and selectivity as well as remarkable detection signals. It enables effective detection of N2H4 in various matrices such as water, food, soil and plant samples thereby significantly expanding the scope of applications for N2H4 probes.

Identification of mutations in viral proteins involved in cell adaptation using a reverse genetic system of the live attenuated hepatitis A virus vaccine H2 strain.

The live attenuated hepatitis A virus vaccine H2 strain was developed by passaging a wild- type H2w isolate in cell cultures. Currently, the mechanism underlying its attenuation phenotype remain largely unknown. In this study, we generated a full-length infectious cDNA clone of the H2 strain using in-fusion techniques. The recovered H2 strain (H2ic) from the cDNA clone exhibited an efficient replication in both the hepatoma cell line Huh7.5.1 and the 2BS cell line used for vaccine production, similar to the parental H2 strain. Additionally, H2ic did not cause disease in Ifnar1-/- C57 mice, consistent with the H2 strain. To explore the cell-adaptive mutations of the H2 strain, chimeric viruses were generated by replacing its non-structural proteins with corresponding regions from H2w using the infectious cDNA clone as a genetic backbone. The chimeric viruses carrying the 3C or 3D proteins from H2w showed decreased replication in Huh7.5.1 and 2BS cell lines compared to H2ic. Other chimeric viruses containing the 2B, 2C, or 3A proteins from H2w failed to be recovered. Furthermore, there were no significant differences in disease manifestation in mice between H2ic and the recovered chimeric viruses. These results demonstrate that adaptive mutations in the 2B, 2C, and 3A proteins are essential for efficient replication of the H2 strain in cell cultures. Mutations in the 3C and 3D proteins contribute to enhanced replication in cell cultures but did not influence the attenuated phenotypes in mice. Together, this study presents the first reverse genetic system of the H2 strain and identifies viral proteins essential for adaptation to cell cultures.

Shallow groundwater table fluctuations weaken nitrogen accumulation in the thin layer vadose zone of cropland around plateau lakes, Southwest China.

Excessive accumulation of nitrogen (N) in the soil profile in the intensive agricultural region will seriously threaten groundwater quality and safety. However, the impact of shallow groundwater table (SGWT) fluctuations driven by seasonal variations on the N accumulation characterizations in the soil profiles has not been well quantified, particularly in the regions with thin layer vadose zone. Through in-situ monitoring and simulation experiments, the changes in the SGWT and N accumulation of soil profile in intensive cropland around 7 plateau lakes in Yunnan were studied during the rainy season (RS) and dry season (DS), and the N loss in soil profile of cropland driven by SGWT fluctuations was estimated. The results showed that the SGWT and N accumulation in soil profile of cropland around the plateau lakes had obvious seasonal variation characteristics. The proportion of N storage in different forms in 60-100 cm soil layer in the RS was greater than that in the DS, particularly the proportion of NH4+-N storage was as high as 55 %, while N accumulation in surface soil was obvious in the DS. Compared with the DS, due to the rising SGWT in the RS, the maximum storages of TN and NO3--N in the 0-100 cm soil layer decreased by17% and 36 %, respectively. The TN loss intensities from the 0-100 cm soil profiles of cropland around Fuxian Lake, Yilong Lake, Qilu Lake, Dianchi Lake, Yangzong Lake, Erhai Lake, and Xingyun Lake were 74, 54, 127, 105, 93, 72 and 207 kg/ha, respectively. Moreover, if the SGWT was <30 cm, the average TN loss intensity and amount could reach 177 kg/ha and 1250 t, respectively. Therefore, the SGWT regulation was one of the key measures to reducing soil N loss from the thin layer vadose zone of cropland around plateau lakes and improving groundwater quality.

High-Throughput Screening and Prediction of Nucleophilicity of Amines Using Machine Learning and DFT Calculations.

Nucleophilic index (NNu) as a significant parameter plays a crucial role in screening of amine catalysts. Indeed, the quantity and variety of amines are extensive. However, only limited amines exhibit an NNu value exceeding 4.0 eV, rendering them potential nucleophiles in chemical reactions. To address this issue, we proposed a computational method to quickly identify amines with high NNu values by using Machine Learning (ML) and high-throughput Density Functional Theory (DFT) calculations. Our approach commenced by training ML models and the exploration of Molecular Fingerprint methods as well as the development of quantitative structure-activity relationship (QSAR) models for the well-known amines based on NNu values derived from DFT calculations. Utilizing explainable Shapley Additive Explanation plots, we were able to determine the five critical substructures that significantly impact the NNu values of amine. The aforementioned conclusion can be applied to produce and cultivate 4920 novel hypothetical amines with high NNu values. The QSAR models were employed to predict the NNu values of 259 well-known and 4920 hypothetical amines, resulting in the identification of five novel hypothetical amines with exceptional NNu values (>4.55 eV). The enhanced NNu values of these novel amines were validated by DFT calculations. One novel hypothetical amine, H1, exhibits an unprecedentedly high NNu value of 5.36 eV, surpassing the maximum value (5.35 eV) observed in well-established amines. Our research strategy efficiently accelerates the discovery of the high nucleophilicity of amines using ML predictions, as well as the DFT calculations.

Conventional ultrasonography enabled with augmented reality needle guidance for percutaneous kidney access: An innovative methodologies randomized controlled trial.

IMPORTANCE: Successful needle puncture of the renal collecting system is a critical but difficult procedure in percutaneous nephrolithotomy (PCNL). Although fluoroscopy and ultrasound are the standard imaging techniques to guide puncture during PCNL, both have known limitations. OBJECTIVE: To assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. DESIGN: This study employed a single-center randomized controlled trial (RCT) design to assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. Conducted between May 2021 and November 2021, the trial utilized computer-generated random numbers for participant allocation to control for selection bias. SETTING: The trial was executed at the *********, which serves as an academic medical center. PARTICIPANTS: All patients who met the inclusion criteria were randomly divided into two groups, with 29 patients in each group. One group underwent PCNL procedures using the new navigation system, while the control group underwent standard ultrasound-guided PCNL procedures. Included patients had renal pelvis or caliceal calculi larger than 2.0 cm in diameter or had multiple or staghorn stones. The puncture procedure was performed with the support of real-time ultrasound imaging and visual guidance displayed on the screen. MAIN OUTCOMES AND MEASURES: The primary outcome was system feasibility and puncture success rate. Secondary outcomes included puncture time, total surgical time, number of attempts, post-procedure complications, and one-year and three-year stone recurrence rates. Stone clearance was defined by postoperative CT. Descriptive statistics summarized patient demographics, stone size, and location. Independent samples t-tests analyzed puncture time and total surgical time. Chi-square or Fisher's exact tests compared stone clearance, complications, socioeconomic status, renal hydronephrosis, stone location, race, and medical history. Linear regression examined the correlation between BMI and puncture time. Significance was set at P<0.05. RESULTS: For all 58 patients undergoing PCNL, needle punctures of the renal collecting system were completed with a success rate of 100%. The average time from planning the puncture protocol to successful puncture was significantly shorter in the AcuSee guidance system group (3.12 min, range 0.2-6.88 min) compared to the standard ultrasound-guided group (7.58 min, range 5.41-10.68 min), representing a reduction of approximately 59%. The total surgical time was also shorter in the AcuSee group for patients with no and mild hydronephrosis (P<0.05). Complication rates were lower in the AcuSee group, with no major complications observed. However, 3 patients in the standard ultrasound-guided group have adverse effects after the PCNL procedure. The one-year stone recurrence rate was significantly lower in the AcuSee group (3.4%) compared to the standard group (24.1%), and the three-year recurrence rate was also lower (6.9% vs. 41.4%). Patient-specific factors such as BMI, renal morphology, and prior surgical history did not significantly affect the performance of the AcuSee system. CONCLUSIONS AND RELEVANCE: We report the first clinical application of a new navigation system for needle puncture in ultrasound-guided PCNL. It has been demonstrated that it is feasible and safe compared to the standard ultrasound-guided group in percutaneous renal puncture. This technology provides intuitive and easy-to-use visual guidance, which may facilitate safe, accurate and fast needle puncture of the kidney.

Hyperhomocysteine promotes cataract development through mTOR-mediated inhibition of autophagy and connexins expression.

AIM: Hyperhomocysteine has been recognized as an independent risk factor of multiple diseases, including several eye diseases. In this study, we aim to investigate whether increased homocysteine (Hcy) is related to cataracts, and to explore whether dysregulation of mTOR-mediated autophagy and connexin expression are underlying mechanisms. METHOD: We first developed a method of liquid chromatography tandem mass spectrometry to accurately measure serum concentrations of Hcy in 287 cataract patients and 334 healthy controls. Next, we treated human lens epithelial (HLC-B3) cells with Hcy at different concentrations and durations, and then analyzed expression of autophagy-related markers and connexins, as well as phosphorylated mTOR (p-mTOR) in these cells by Western blotting. Formation of autophagic vacuoles and intracellular Ca2+ in the Hcy-treated cells were observed by fluorescence microscopy. Further, we performed a rescue experiment in the Hcy-treated HLC-B3 cells by pre-incubation with rapamycin, an mTOR inhibitor. RESULTS: The serum levels of Hcy in patients with cataracts were significantly increased compared to those in healthy controls. In cultured HLC-B3 cells, expression of autophagy related markers (LC3B and Beclin1) and connexins (Cx43 and Cx50) was inhibited by Hcy treatment in a dose- and duration-dependent manner. Accumulation of Ca2+ in the Hcy-treated lens epithelial cells was observed as a consequence of reduced connexin expression. Meanwhile, expression of p-mTOR increased, representing up-regulation of the mTOR pathway. Importantly, inhibition of autophagy and connexin expression due to hyperhomocysteine was rescued via mTOR suppression by pretreatment with rapamycin in HLC-B3 cells. CONCLUSION: Our results demonstrate that hyperhomocysteine might promote cataract development through two mTOR-mediated pathways in the lens epithelial cells: 1) dysregulation of autophagy and 2) accumulation of intracellular calcium via decreased connexin expression.

A ratiometric fluorescent probe for selective detection of hypochlorite (ClO-) and gallium (III) (Ga3+) ions in environmental and food samples.

Hypochlorite (ClO-) and gallium (Ⅲ) ions (Ga3+) have extensive applications in various human industries and daily activities. However, their inherent toxicity poses significant risks to environmental preservation and human well-being. Hence, the development of reliable and handy detection tools for ClO- and Ga3+ in the environment and food is crucial. In this study, a ratiometric fluorescent probe was prepared based on benzothiazolaldehyde and pyridine-2-carboxylic acid hydrazide, which exhibited exceptional performance characteristics for the selective detection of ClO- and Ga3+. These features include high specificity, low detection limits (0.28 µM for ClO-, 0.13 µM for Ga3+), mild pH conditions (pH 4-11 for ClO-, pH 6-11 for Ga3+), fast response time (within 30 s), as well as versatile applicability across different matrices such as water, soil, food, and plant samples. Additionally, this probe can be used with a smartphone color recognition app. The probe offers a convenient and effective tool for the detection of ClO- and Ga3+, demonstrating its potential application value in environmental monitoring and food safety.

DNA Origami-Constructed Nanotapes for Sunitinib Adsorption and Inhibition of Renal Clear Carcinoma Cells.

Sunitinib (SUN) is a first-line drug for the treatment of renal clear carcinoma cells by targeting receptor tyrosine kinases (RTK) on the cell membrane. However, the effective delivery of SUN to the cell membrane remains a significant challenge. In this study, we fabricated precisely structured DNA nanotapes with strong surface SUN adhesion, enabling RTK inhibition of renal clear carcinoma cells. In our design, the precisely assembled linear topological six-helical-bundle DNA origami serves as the framework, and positively charged chitosan is adsorbed onto the DNA origami surface, thereby forming DNA nanotapes. The SUN was efficiently loaded onto the surface of the DNA nanotapes by electrostatic interaction. We found that DNA nanotapes exhibit excellent stability in serum. Importantly, DNA nanotapes carrying SUN can achieve prolonged cell membrane retention and inhibit RTK, thereby enhancing cytotoxicity toward 786-0 cells. Taken together, this study provides a promising candidate platform for the efficient delivery of cell membrane receptor inhibitors in anticancer therapy.

DNA methylation profiling deciphers three EMT subtypes with distinct prognoses and therapeutic vulnerabilities in breast cancer.

Background: Epithelial-mesenchymal transition (EMT), deemed a pivotal hallmark of tumours, is intricately regulated by DNA methylation and encompasses multiple states along tumour progression. The potential mechanisms that drive the intrinsic heterogeneity of breast cancer (BC) via EMT transformation have not been identified, presenting a significant obstacle in clinical diagnosis and treatment. Methods: A total of 7,602 patients have been included in this study. We leveraged integrated multiomics data (epigenomic, genomic, and transcriptomic data) to delineate the comprehensive landscape of EMT in BC. Subsequently, a subtyping classifier was developed through a machine learning framework proposed by us. Results: We classified the BC samples into three methylation-driven EMT subtypes with distinct features, namely, C1 (the mammary duct development subtype with TP53 activation), C2 (the immune infiltration subtype with high TP53 mutation), and C3 (the ERBB2 amplification subtype with an unfavorable prognosis). Specifically, patients with the C1 subtype might respond to endocrine therapy or the p53-MDM2 antagonist nutlin-3. Patients with the C2 subtype might benefit from combined therapeutic regimens involving radiotherapy, PARP inhibitors, and immune checkpoint blockade therapy. Patients with the C3 subtype might benefit from anti-HER2 agents such as lapatinib. Notably, to increase the clinical applicability of the EMT subtypes, we devised a 96-gene panel-based classifier via a machine learning framework. Conclusions: Our study identified three methylation-driven EMT subtypes with distinct prognoses and biological traits to capture heterogeneity in BC and provided a rationale for the use of this classification as a powerful tool for developing new strategies for clinical trials.

Floatable Termination-Vacant MXene Architecture for High-Performance and Cost-Effective Photothermal Dehydrogenation.

Liquid hydrogen carriers have garnered considerable interest in long-distance and large-scale hydrogen storage owing to their exceptional hydrogen storage density, safety, and compatibility. Nonetheless, their practical application is hampered by the low hydrogen production rate and high cost, stemming from poor thermal utilization and heavy reliance on noble metals in solar bulk dehydrogenation platforms. To conquer these challenges, we devise an economical all-in-one architecture comprising the photothermal catalytic termination-vacant MXene and a highly insulated melamine substrate. This design floats on the air-reactant interface to efficiently drive solar interfacial dehydrogenation. The melamine enables interfacial heat localization to improve the thermal utilization, providing a high reaction temperature. Meanwhile, the MXene with termination vacancies exposes rich active sites for formic acid dehydrogenation, and simultaneously high performance and cost-effectiveness can be realized. This work offers fresh perspectives on the design and application of photothermal catalytic MXene, broadening the prospects for hydrogen storage using liquid hydrogen carriers.

A General Approach for the Synthesis of Cyanoisopropyl Bicyclo[1.1.1]pentane (BCP) Motifs by Energy Transfer Process.

Bicyclo[1.1.1]pentane (BCP) heteroaryls make up an important class of BCP derivatives in drug discovery. Herein, we report the visible-light-mediated synthesis of cyanoisopropyl BCP-heteroaryls motifs from N-containing heterocycles, [1.1.1]propellane, and AIBN (2,2'-azobis(isobutyronitrile)) through three-component cascade reaction. Importantly, this protocol is compatible with pyrazinones, quinoxaline-2(1H)-one, azauracils, quinoline derivatives, and imidazo[1,2-b]pyridazine, as well as various phenyl disulfide derivatives; thus, this operationally simple and general methodology could enable rapid library generation of sought-after BCP derivatives for drug development.

Exosomal miR-486 derived from bone marrow mesenchymal stem cells promotes angiogenesis following cerebral ischemic injury by regulating the PTEN/Akt pathway.

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been shown to promote angiogenesis after ischemic stroke, in which microRNAs (miRs) are believed to play an important role in exosome-mediated therapeutic effects, though the mechanism is still not clear. In this study, a series of molecular biological and cellular assays, both in vitro and in vivo, were performed to elucidate the role of exosomal miR-486 in angiogenesis following cerebral ischemic and its molecular mechanisms. Our results revealed that BMSC-Exos significantly improved neurological function and increased microvessel density in ischemic stroke rats. In vitro assays showed that BMSC-Exos promoted the proliferation, migration, and tube formation ability of oxygen-glucose deprivation/reoxygenation (OGD/R) injured rat brain microvascular endothelial cells (RBMECs). Importantly, BMSC-Exos increased the expression of miR-486 and phosphorylated protein kinase B (p-Akt) and down-regulated the protein level of phosphatase and tensin homolog (PTEN) in vivo and in vitro. Mechanistic studies demonstrated that transfection with miR-486 mimic enhanced RBMECs angiogenesis and increased p-Akt expression, while inhibited PTEN expression. On the other hand, the miR-486 inhibitor induced an opposite effect, which could be blocked by PTEN siRNA. It was thus concluded that exosomal miR-486 from BMSCs may enhance the functional recovery by promoting angiogenesis following cerebral ischemic injury, which might be related to its regulation of the PTEN/Akt pathway.

Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients.

BACKGROUND: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. METHODS: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. RESULTS: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384-73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045-28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48-49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25-25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48-12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09-27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798-0.934) with a sensitivity of 0.761 and specificity of 0.869. CONCLUSION: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.