A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice.

Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. + i.m., i.m. + i.n., i.n. + i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. + i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. + i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus vector to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.

Efficient molecular conformation generation with quantum-inspired algorithm.

CONTEXT: Conformation generation, also known as molecular unfolding (MU), is a crucial step in structure-based drug design, remaining a challenging combinatorial optimization problem. Quantum annealing (QA) has shown great potential for solving certain combinatorial optimization problems over traditional classical methods such as simulated annealing (SA). However, a recent study showed that a 2000-qubit QA hardware was still unable to outperform SA for the MU problem. Here, we propose the use of quantum-inspired algorithm to solve the MU problem, in order to go beyond traditional SA. We introduce a highly compact phase encoding method which can exponentially reduce the representation space, compared with the previous one-hot encoding method. For benchmarking, we tested this new approach on the public QM9 dataset generated by density functional theory (DFT). The root-mean-square deviation between the conformation determined by our approach and DFT is negligible (less than about 0.5Å), which underpins the validity of our approach. Furthermore, the median time-to-target metric can be reduced by a factor of five compared to SA. Additionally, we demonstrate a simulation experiment by MindQuantum using quantum approximate optimization algorithm (QAOA) to reach optimal results. These results indicate that quantum-inspired algorithms can be applied to solve practical problems even before quantum hardware becomes mature. METHODS: The objective function of MU is defined as the sum of all internal distances between atoms in the molecule, which is a high-order unconstrained binary optimization (HUBO) problem. The degree of freedom of variables is discretized and encoded with binary variables by the phase encoding method. We employ the quantum-inspired simulated bifurcation algorithm for optimization. The public QM9 dataset is generated by DFT. The simulation experiment of quantum computation is implemented by MindQuantum using QAOA.

Development and validation of a deep learning-based model to predict response and survival of T790M mutant non-small cell lung cancer patients in early clinical phase trials using electronic medical record and pharmacokinetic data.

Background: Epidermal growth factor receptor (EGFR) T790M mutation is the standard predictive biomarker for third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. While not all T790M-positive patients respond to third-generation EGFR-TKIs and have a good prognosis, it necessitates novel tools to supplement EGFR genotype detection for predicting efficacy and stratifying EGFR-mutant patients with various prognoses. Mixture-of-experts (MoE) is designed to disassemble a large model into many small models. Meanwhile, it is also a model ensembling method that can better capture multiple patterns of intrinsic subgroups of enrolled patients. Therefore, the combination of MoE and Cox algorithm has the potential to predict efficacy and stratify survival in non-small cell lung cancer (NSCLC) patients with EGFR mutations. Methods: We utilized the electronic medical record (EMR) and pharmacokinetic parameters of 326 T790M-mutated NSCLC patients, including 283 patients treated with Abivertinib in phase I (n=177, for training) and II (n=106, for validation) clinical trials and an additional validation cohort 2 comprising 43 patients treated with BPI-7711. Furthermore, 18 patients underwent whole-exome sequencing for biological interpretation of CoxMoE. We evaluated the predictive performance for therapeutic response using the area under the curve (AUC) and the Concordance index (C-index) for progression-free survival (PFS). Results: CoxMoE exhibited AUCs of 0.73-0.83 for predicting efficacy defined by best overall response (BoR) and achieved C-index values of 0.64-0.65 for PFS prediction in training and validating cohorts. The PFS of 198 patients with a low risk [median, 6.0 (range, 1.0-23.3) months in the abivertinib treated cohort; median 16.5 (range, 1.4-27.4) months in BPI-7711 treated cohort] of being non-responder increased by 43% [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.40-0.78; P=0.0013] and 50% (HR, 0; 95% CI, 0-0; P=0.01) compared to those at high-risk [median, 4.2 (range, 1.0-35) months in the abivertinib treated cohort; median, 11.0 (range, 1.4-25.1) months in BPI-7711 treated cohort]. Additionally, activated partial thromboplastin time (APTT), creatinine clearance (Ccr), monocyte, and steady-state plasma trough concentration utilited to construct model were found significantly associated with drug resistance and aggressive tumor pathways. A robust correlation was observed between APTT and Ccr with PFS (log-rank test; P<0.01) and treatment response (Wilcoxon test; P<0.05), respectively. Conclusions: CoxMoE offers a valuable approach for patient selection by forecasting therapeutic response and PFS utilizing laboratory tests and pharmacokinetic parameters in the setting of early-phase clinical trials. Simultaneously, CoxMoE could predict the efficacy of third-generation EGFR-TKI non-invasively for T790M-positive NSCLC patients, thereby complementing existing EGFR genotype detection.

The Index sAGP is Valuable for Distinguishing Atypical Hepatocellular Carcinoma from Atypical Benign Focal Hepatic Lesions.

Purpose: The differential diagnosis of atypical hepatocellular carcinoma (aHCC) and atypical benign focal hepatic lesions (aBFHL) usually depends on pathology. This study aimed to develop non-invasive approaches based on conventional blood indicators for the differential diagnosis of aHCC and aBFHL. Patients and Methods: Hospitalized patients with pathologically confirmed focal hepatic lesions and their clinical data were retrospectively collected, in which patients with HCC with serum alpha-fetoprotein (AFP) levels of ≤200 ng/mL and atypical imaging features were designated as the aHCC group (n = 224), and patients with benign focal hepatic lesions without typical imaging features were designated as the aBFHL group (n = 178). The performance of indexes (both previously reported and newly constructed) derived from conventional blood indicators by four mathematical operations in distinguishing aHCC and aBFHL was evaluated using the receiver operating characteristic (ROC) curve and diagnostic validity metrics. Results: Among ten previously reported derived indexes related to HCC, the index GPR, the ratio of γ-glutamyltransferase (GGT) to platelet (PLT), showed the best performance in distinguishing aHCC from aBFHL with the area under ROC curve (AUROC) of 0.853 (95% CI 0.814-0.892), but the other indexes were of little value (AUROCs from 0.531 to 0.700). A new derived index, sAGP [(standardized AFP + standardized GGT)/standardized PLT], was developed and exhibited AUROCs of 0.905, 0.894, 0.891, 0.925, and 0.862 in differentiating overall, BCLC stage 0/A, TNM stage I, small, and AFP-negative aHCC from aBFHL, respectively. Conclusion: The sAGP index is an efficient, simple, and practical metric for the non-invasive differentiation of aHCC from aBFHL.

BZW1 is a prognostic and immunological biomarker in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is the most common malignant tumor of the digestive system and is called the "king of cancer" because it has been labeled with high malignancy, rapid progression, poor survival, and poor prognosis. Previously, it was reported that the basic leucine zipper and W2 domains 1 (BZW1) is involved in the progression of many tumors. However, its research in digestive system tumors such as pancreatic cancer is rarely studied. To explore potential biomarkers related to survival and prognosis of pancreatic cancer and provide a new targeted therapy for it. We first analyzed the mRNA and protein expression of BZW1 in pancreatic cancer. We then explored the correlation of BZW1 with survival prognosis and immune infiltration in pancreatic cancer patients. Finally, we explored BZW1-related gene enrichment analysis, including protein-protein interaction networks, gene ontology functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The mRNA and protein expression of the BZW1 gene in pancreatic cancer tissues were higher than those in adjacent normal tissues, and pancreatic cancer patients with high BZW1 expression had a poor prognosis. In addition, the expression of BZW1 was positively or negatively correlated with different immune cells of pancreatic cancer, such as CD4 + T lymphocytes, CD8 + T lymphocytes, B cells, macrophages, neutrophils, etc. Correlation enrichment analysis showed that we obtained 50 available experimentally determined BZW1-binding proteins and 100 targeted genes related to BZW1, and the intersection genes were eukaryotic translation termination factor 1 and Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3. Moreover, there was a positive correlation between BZW1 and eukaryotic translation termination factor 1 and Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 genes in pancreatic cancer. Gene ontology enrichment analysis showed BZW1 was mainly related to biological processes such as "mRNA processing," "RNA splicing," "regulation of translational initiation," and "activation of innate immune response." The results of Kyoto Encyclopedia of Genes and Genomes pathway analysis further indicated that BZW1 may be involved in pancreatic carcinogenesis through the "spliceosome" and "ribosome." The BZW1 gene may be a potential immunotherapy target and a promising prognostic marker for pancreatic cancer.

TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Hydrophobicity Tuning of Cationic Polyaspartamide Derivatives for Enhanced Antisense Oligonucleotide Delivery.

Various cationic polymers are used to deliver polyplex-mediated antisense oligonucleotides (ASOs). However, few studies have investigated the structural determinants of polyplex functionalities in polymers. This study focused on the polymer hydrophobicity. A series of amphiphilic polyaspartamide derivatives possessing various hydrophobic (R) moieties together with cationic diethylenetriamine (DET) moieties in the side chain (PAsp(DET/R)s) were synthesized to optimize the R moieties (or hydrophobicity) for locked nucleic acid (LNA) gapmer ASO delivery. The gene knockdown efficiencies of PAsp(DET/R) polyplexes were plotted against a hydrophobicity parameter, logD7.3, of PAsp(DET/R), revealing that the gene knockdown efficiency was substantially improved by PAsp(DET/R) with logD7.3 higher than -2.4. This was explained by the increased polyplex stability and improved cellular uptake of ASO payloads. After intratracheal administration, the polyplex samples with a higher logD7.3 than -2.4 induced a significantly higher gene knockdown in the lung tissue compared with counterparts with lower hydrophobicity and naked ASO. These results demonstrate that the hydrophobicity of PAsp(DET/R) is crucial for efficient ASO delivery in vitro and in vivo.

Effect of membrane thermal conductivity on ion current rectification in conical nanochannels under asymmetric temperature.

Nowadays, there have been extensively theoretical studies on the phenomenon of ion current rectification (ICR) induced by the asymmetric electrical double layer (EDL). As a key factor influencing the behavior of ion transport, temperature is given high priority by researchers. The thermal conductivity of the material commonly employed to prepare nanopores is 2-3 times higher than that of liquid solutions, which may affect ion transport within the nanochannel. However, it is often neglected in previous studies. Thus, we investigate the effect of membrane thermal conductivity on the ICR in conical nanochannels under asymmetric temperature. Based on the PNP-NS theoretical model, the ion current, the rectification ratio, as well as the temperature and ion concentration distributions along the nanochannel are calculated. It is found that the thermal conductivity of the solid membrane noticeably affects the temperature distribution across the nanochannel, altering the ion transport behavior. Larger membrane thermal conductivity tends to homogenize the temperature distribution in the nanochannel, leading to a decline of ionic thermal down-diffusion by a positive temperature difference and ionic thermal up-diffusion by a negative temperature difference, with the former promoting and the latter inhibiting ion current. As a result, the rectification ratio decreases under the positive temperature difference and increases under the negative temperature difference as the thermal conductivity of the membrane increases. These studies will be instructive for the design of nanofluidic diodes and biosensors.

Update on Nonhuman Primate Models of Brain Disease and Related Research Tools.

The aging of the population is an increasingly serious issue, and many age-related illnesses are on the rise. These illnesses pose a serious threat to the health and safety of elderly individuals and create a serious economic and social burden. Despite substantial research into the pathogenesis of these diseases, their etiology and pathogenesis remain unclear. In recent decades, rodent models have been used in attempts to elucidate these disorders, but such models fail to simulate the full range of symptoms. Nonhuman primates (NHPs) are the most ideal neuroscientific models for studying the human brain and are more functionally similar to humans because of their high genetic similarities and phenotypic characteristics in comparison with humans. Here, we review the literature examining typical NHP brain disease models, focusing on NHP models of common diseases such as dementia, Parkinson's disease, and epilepsy. We also explore the application of electroencephalography (EEG), magnetic resonance imaging (MRI), and optogenetic study methods on NHPs and neural circuits associated with cognitive impairment.

Long noncoding RNA XLOC_006786 inhibits the proliferation, invasion and metastasis of osteosarcoma cells through NOTCH3 signaling pathway by targeting miR-491-5p.

Recent research has indicated that Long noncoding RNAs (LncRNAs) are crucial in many disorders, especially tumors. However, the exact role of LncRNA XLOC_006786 (LncRNA-SPIDR-2:1) in malignancies, especially in human osteosarcoma, is unclear. The results of RT‒qPCR, western blotting, CCK-8 assays, and Transwell assays showed that LncRNA XLOC_006786 inhibited osteosarcoma cell proliferation, invasion, and migration, indicating that it may be a tumor suppressor gene in osteosarcoma. We found that LncRNA XLOC_006786 negatively regulated NOTCH3, which is an oncogenic gene in osteosarcoma, as we previously reported. Bioinformatics analysis showed that miR-491-5p may be a direct target of LncRNA XLOC_006786, while NOTCH3 is a key target of miR-491-5p. Then, we verified that LncRNA XLOC_006786 could prevent lung metastatic osteosarcoma in vivo. Taken together, our research showed that LncRNA XLOC_006786 suppresses osteosarcoma proliferation, invasion, and metastasis through the NOTCH3 signaling pathway by targeting miR-491-5p.

[Research Status and Trend Analysis of Environmental and Health Risk and Control of Persistent, Mobile, and Toxic Chemicals].

Persistent, mobile, and toxic or very persistent and very mobile (PMT/vPvM) chemicals have been widely detected in surface water, groundwater, and drinking water around the world and are important emerging contaminants that may significantly affect human health and the environment in the future. According to the identification criteria proposed by the European Union, there are thousands of PMT/vPvM substances in existing chemicals, covering a wide range of applications, including dozens of high-yield industrial chemicals such as melamine. PMT/vPvM chemicals can be discharged into the environment through farmland runoff, industrial wastewater, and domestic sewage, and sewage treatment plants are currently considered to be their main discharge route. It is difficult to effectively remove PMT/vPvM chemicals through the current conventional water treatment technology; they can exist in the water circulation system of the urban human settlement environment for a long time, endangering the safety of drinking water and the ecosystem. The European Union has taken the lead in introducing PMT/vPvM chemicals specifically into the priority areas of the current chemical risk management system. At present, there are still many potential PMT/vPvM chemicals in the environment, and their monitoring methods need to be further improved. It will take time for the identification of substances, the scope of categories, and the establishment of lists. Studies on the environmental fate and exposure of PMT/vPvM in various regions of the world are still very limited, and research on the potential, long-term ecotoxicity, and human health hazard effects remains scarce. At the same time, the research and development of substitute or alternative technologies, as well as environmental engineering treatment technologies such as sewage treatment and contaminated site remediation, will become an urgent need for future PMT/vPvM risk scientific research and management decisions.

A MnAl double adjuvant nanovaccine to induce strong humoral and cellular immune responses.

At present, the most widely used aluminum adjuvants have poor ability to induce effective Th1 type immune responses. Existing evidence suggests that manganese is a potential metal adjuvant by activating cyclic guanosine phospho-adenosine synthase (cGAS)-interferon gene stimulator protein (STING) signaling pathway to enhance humoral and cellular immune response. Hence, the effective modulation of metal components is expected to be a new strategy to improve the efficiency of vaccine immunization. Here, we constructed a manganese and aluminum dual-adjuvant antigen co-delivery system (MnO2-Al-OVA) to enhance the immune responses of subunit vaccines. Namely, the aluminum hydroxide was first fused on the surface of the pre-prepared MnO2 nanoparticles, which were synthesized by a simple redox reaction with potassium permanganate (KMnO4) and oleic acid (OA). The engineered MnO2-Al-OVA could remarkably promote cellular internalization and maturation of dendritic cells. After subcutaneous vaccination, MnO2-Al-OVA rapidly migrated into the lymph nodes (LNs) and efficiently activate the cGAS-STING pathway, greatly induced humoral and cellular immune responses. Of note, our findings underscore the importance of coordination manganese adjuvants in vaccine design by promoting the activation of the cGAS-STING-IFN-I pathway. With a good safety profile and facile preparation process, this dual-adjuvant antigen co-delivery nanovaccine has great potential for clinical translation prospects.

Kinsenoside alleviates oxidative stress-induced blood-brain barrier dysfunction via promoting Nrf2/HO-1 pathway in ischemic stroke.

An ischemic stroke usually causes blood-brain barrier (BBB) damage and excessive oxidative stress (OS) levels. Kinsenoside (KD), a major effective compound extracted in Chinese herbal medicine Anoectochilus roxburghii (Orchidaceae), has anti-OS effects. The present study focused on exploring KD's protection against OS-mediated cerebral endothelial cell damage and BBB damage within the mouse model. Intracerebroventricular administration of KD upon reperfusion after 1 h ischemia decreased infarct volumes, neurological deficit, brain edema, neuronal loss, and apoptosis 72 h post-ischemic stroke. KD improved BBB structure and function, as evidenced by a lower 18F-fluorodeoxyglucose pass rate of the BBB and upregulation of tight junction (TJ) proteins such as occludin, claudin-5, and zonula occludens-1 (ZO-1). KD protected bEnd.3 endothelial cells from oxygen and glucose deprivation/reoxygenation (OGD/R) injury in an in-vitro study. Meanwhile, OGD/R reduced transepithelial electronic resistance, whereas KD significantly increased TJ protein levels. Furthermore, based on in-vivo and in-vitro research, KD alleviated OS in endothelial cells, which is related to nuclear factor, erythroid 2 like 2 (Nrf2) nuclear translocation as well as Nrf2/haem oxygenase 1 signaling protein stimulation. Our findings demonstrated that KD might serve as a potential compound for treating ischemic stroke involving antioxidant mechanisms.

Rat tight junction proteins are disrupted after subchronic exposure to okadaic acid.

Okadaic acid (OA), a lipophilic phycotoxin distributed worldwide, causes diarrheic shellfish poisoning and even leads to tumor formation. Currently, the consumption of contaminated seafood is the most likely cause of chronic OA exposure, but there is a serious lack of relevant data. Here, the Sprague-Dawley rats were exposure to OA by oral administration at 100 µg/kg body weight, and the tissues were collected and analyzed to assess the effect of subchronic OA exposure. The results showed that subchronic OA administration disturbed colonic mucosal integrity and induced colitis. The colonic tight junction proteins were disrupted and the cell cycle of colonic epithelial cells was accelerated. It is inferred that disruption of the colonic tight junction proteins might be related to the development of chronic diarrhea by affecting water and ion transport. Moreover, the accelerated proliferation of colonic epithelial cells indicated that subchronic OA exposure might promote the restitution process of gut barrier or induce tumor promoter activity in rat colon.

α-Cyperone ameliorates depression in mammary gland hyperplasia and chronic unpredictable mild stress rat by regulating hormone, inflammation, and oxidative stress.

BACKGROUND: Hyperplasia of mammary gland (HMG) is caused by endocrine disorders, and patients are prone to anxiety and depression. α-Cyperone has a variety of pharmacological activities including antidepressant. The purpose of this study was to explore the effect and its possible mechanism of α-Cyperone on HMG-associated depression rats. METHODS: The depression model was constructed using chronic unpredictable mild stress (CUMS), while the HMG model was induced by estrogen, with or without α-Cyperone intervention. The effect of α-Cyperone on the depression-like phenotype of model rats was measured by sucrose preference test (SPT), forced swim test (FST), and open field test (OFT). Dendritic spines density in ventral medial prefrontal cortex (vmPFC) neurons was evaluated by Golgi staining. The second pair of nipple height, diameter, organ index, and oxidative stress-related factors were analyzed. Serum sex hormone concentration, histopathological changes, inflammatory factor expression, and p65 were evaluated by enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, real-time quantitative PCR and western blot, respectively. RESULTS: The sucrose preference rate, dendritic spine density decreased, and immobility time increased in CUMS rats; α-Cyperone reversed the effect of CUMS on depression-like behavior and dendritic spine density in rats. α-Cyperone reduced nipple height and diameter, uterine index, estradiol concentration, increased ovary, thymus, spleen index, progesterone, and testosterone concentration, relieved pathological damage, oxidative stress, depression-like behavior, and inflammatory reaction in HMG combine CUMS rats. In addition, α-Cyperone inhibited the phosphorylation of p65 in HMG and CUMS rats. CONCLUSIONS: α-Cyperone has an effective therapeutic effect on HMG combined with CUMS rats.

In-situ construction of fluorescent probes for hydrogen peroxide detection in mitochondria and lysosomes with on-demand modular assembling and double turn-on features.

Due to the diverse H2O2 distribution in organelles, fluorescent probes were usually required to be prepared separately, which limited the convenience and practicability. Herein, we reported a flexible strategy to in-situ construct H2O2 fluorescent probes in different organelles. A tetrazine fused probe TP was developed with rapid click reaction capacity and sensitive H2O2 response. When treated with H2O2, the turn-on fluorescence was effectively quenched by the tetrazine part. Only after click reaction with dienophiles, the fluorescence resumed. In application, cells were firstly treated with triphenylphosphorus tagged norbornene (TPP-NB) to label mitochondria, which was followed by the introduction of probe TP to trigger click reaction. The in-situ constructed probe P1 served as a local H2O2 sensor. In a similar way, probe P2 was in-situ constructed in lysosomes via probe TP and morpholine tagged norbornene (MP-NB). With this on-demand modular assembling and double turn-on features, our strategy to construct fluorescent probes presented high flexibility and anti-interference performance, which was expected to inspired more applications in biological studies.

Clinical analysis of laparoscopic treatment of chronic traumatic diaphragmatic hernia in 29 cases / 中华外科杂志

Objective: To examine the safety and effectiveness of laparoscopic individualized surgical treatment for chronic traumatic diaphragmatic hernia (CTDH). Methods: The clinical data and follow-up data of 29 CTDH cases admitted to the Qilu Hospital of Shandong University or the First Affiliated Hospital of Shandong First Medical University from June 2015 to January 2023 were retrospectively analyzed. There were 21 males and 8 females, aged (49.4±17.8) years (range: 19 to 79 years). The main clinical manifestations were symptoms of the digestive system and respiratory system, and only 4 cases were asymptomatic. All patients received laparoscopic treatment (conversion to open surgery was not excluded). Intraoperative exploration (location of the hernia, contents of the hernia, diameter of the hernia ring), surgical conditions (surgical repair plan, operation time, blood loss, postoperative complications) and postoperative follow-up were analyzed and discussed. Results: Laparoscopic repair was successfully completed in 27 cases, including simple suture in 6 cases, suture and patch repair in 17 cases, the anterior abdominal wall muscle flap reversal suture and patch repair of in 3 cases, and patch bridge repair in 1 case. The operation time was (112.8±44.7) minutes (range: 60 to 200 minutes). The amount of bleeding (M(IQR)) was 35 (58) ml (range: 10 to 300 ml). The other 2 patients were converted to laparotomy. Except for one patient with transverse colon strangulation necrosis who died of aggravated pulmonary infection after surgery, the remaining 28 patients were discharged successfully. The follow-up time was 36 (24) months (range: 1 to 60 months). During the follow-up period, only two patients had occasional left upper abdominal discomfort. Twenty-seven patients with left diaphragmatic hernia had no recurrence, and the symptoms of 1 patient with right diaphragmatic hernia were relieved. Conclusion: Customized laparoscopic surgical repair for CTDH according to the location and size of the diaphragmatic defect can achieve good surgical results.

Endovascular treatment vs drug therapy alone in patients with mild ischemic stroke and large infarct cores.

BACKGROUND: Treatment decision making is strictly associated with the outcomes in patients with ischemic stroke who show a large core infarct. Medical care alone may result in suboptimal treatment efficacy, and endovascular treatment may be accompanied by safety issues. Whether endovascular treatment is superior to medical care is not well investigated in the clinical studies. AIM: To investigate the efficacy of endovascular treatment and drug therapy alone in mild ischemic stroke patients with large infarct cores. METHODS: Fifty patients with mild ischemic stroke and 50 patients with acute ischemic stroke caused by anterior large vessel occlusion were selected at the First Affiliated Hospital of Hebei North University between January 2021 and December 2021. Patients were divided into an endovascular therapy group and a drug therapy group according to different treatment methods. In the endovascular therapy group, there were 28 patients with minor stroke and 22 patients with large infarct cores. The drug therapy group had 22 patients with minor stroke and 28 patients with large infarct cores. The National Institutes of Health Stroke Scale (NIHSS) scores were collected and compared between the two groups immediately after the operation and 24 h and 7 d after the operation. The modified Rankin scale (mRS) and/or activity of daily living were assessed at hospital discharge. RESULTS: There was no significant difference in NIHSS scores between the two groups before the operation (P > 0.05). NIHSS scores were lower in the endovascular therapy group than in the drug therapy group at 24 h and 7 d after the operation and at hospital discharge (all P < 0.05). The incidence of early neurologic deterioration was significantly lower in the endovascular therapy group than in the drug therapy group (P < 0.05). At hospital discharge, the mRS score was lower in the endovascular treatment group than in the drug therapy group, and the activity of daily living score was better in the endovascular treatment group than in the drug therapy group (all P < 0.05). During a follow-up of 3 mo, 17 patients (34.0%) had good prognosis (mRS ≤ 2), 33 patients (66.0%) had poor prognosis (mRS > 2), and 11 patients (22.0%) died. In the medical treatment group, 16 patients (mRS ≤ 2) had good prognosis (32.0%), 34 patients (mRS > 2) had poor prognosis (68.0%), and 14 patients (28.0%) died. There was no significant difference in prognosis and mortality between the two groups (P > 0.05). CONCLUSION: Endovascular therapy can improve NIHSS score and mRS score in patients with mild ischemic stroke and large infarct cores. It is suitable for clinical application.

Artificial Tactile Recognition Enabled by Flexible Low-Voltage Organic Transistors and Low-Power Synaptic Electronics.

The advancement of self-powered intelligent strain systems for human-computer interaction is crucial toward wearable and energy-saving applications. Simultaneously, lowering operating voltage and thus reducing power consumption are of particular interests. A brain-like smart synaptic hardware system is considered as a promising candidate for low-power, parallel computing and learning processes. However, the combination of low-voltage organic transistors and energy efficient smart synapse hardware systems driven by a tactile signal has been hindered by the limited materials and technology. Here, by employing an elastomeric copolymer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) with a high HFP content of 25 mol %, flexible, low-voltage transistors (|VG| ≤ 3 V) and a low energy consumption synapse ≤ 9.2 × 10-17 J are devised simultaneously, along with the lowest quality factor (R = Pw × VG, 2.76 × 10-16 J V). Furthermore, based on the low voltage and low power consumption characteristics, flexible artificial tactile recognition system and Morse code recognition are established without any computing supporting. Mechanical flexibility, cycling stability, image contrast enhancement functions, and simulated pattern recognition accuracy of the multilayer perceptron neural network are also simulated. This work recommends a route of exploiting low voltage, low power consumption synaptic systems and smart human-machine interfaces with low energy loss based on flexible organic synaptic transistors.