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Avian hepatitis E virus (HEV) has resulted in significant economic losses in the poultry industry. There is currently no commercial vaccination available to prevent avian HEV infection. Previously, a novel epitope ( 601 TFPS 604 ) was discovered in the ORF2 protein of avian HEV. In this study, peptides were synthesized and assessed for their ability to provide immunoprotecting against avian HEV infection in poultry. Twenty-five Hy-Line Variety Brown laying hens were randomly divided into five groups; groups 1 to 3 respectively immunized with RLLDRLSRTFPS, PETRRLLDRLSR (irrelevant peptide control), or truncated avian HEV ORF2 protein (aa 339-606), while group 4 (negative control) was mock-immunized with PBS and group 5 (normal control) was not immunized or challenged. After the challenge, all hens in groups 2 and 4 showed seroconversion, fecal virus shedding, viremia, alanine aminotransferase (ALT) level increasing, liver lesions and HEV antigen in the liver. There were no pathogenic effects in other groups. Collectively, all of these findings showed that hens were completely protected against avian HEV infection when they were immunized with the peptide containing TFPS of the avian HEV ORF2 protein., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prostate cancer therapies against androgen receptor (AR) eventually develop lethal resistance; thus, exploring new therapeutic approaches is urgent for prostate cancer treatment. Acetyltransferase p300/CBP are key coactivators for AR-mediated transcription and represent promising therapeutic targets to inhibit AR activity in prostate cancer. We describe the design synthesis and evaluation of a new class of p300/CBP PROTAC degraders. We identified an excellent p300/CBP degrader MJP6412 , which effectively induced degradation of p300/CBP proteins, downregulated AR target genes, and inhibited cell growth of human prostate cancer cell lines and enzalutamide-resistant cells with IC 50 even at nanomolar concentrations. Furthermore, MJP6412 demonstrated significant inhibition of tumor growth in a VCaP xenograft model. Collectively, MJP6412 is a promising lead compound for the treatment of prostate cancer, especially enzalutamide-resistant prostate cancer.

Objective: To analyze changes in renal function and associated risk factors in patients with bladder cancer undergoing robot-assisted radical cystectomy (RARC) with intracorporeal or extracorporeal urinary diversion (ICUD or ECUD)., Methods: Clinical-pathological data was extracted from electronic medical records of 266 patients with bladder cancer who underwent RARC at our institution between August 2015 and August 2022. Postoperative renal function was assessed using the estimated glomerular filtration rate (eGFR)., Result: Patients were classified into ECUD and ICUD groups based on the surgical approach. Significant differences in eGFR were observed between the two groups at 1, 2, and 3 years postoperatively. Moreover, 112 patients (42.1%) experienced long-term renal function injury. Independent risk factors for long-term renal function injury included the type of surgical approach, ureteroenteric anastomotic strictures, and pathological stage T3 or above. In terms of short-term renal function, 30 cases of acute kidney injury (AKI) were observed, with an incidence rate of 11.3%. No difference in AKI incidence was found between the groups., Conclusions: Postoperative AKI and chronic kidney injury are prevalent complications following RC. This study highlights that pathological stage, ureteroenteric anastomotic strictures, and ECUD significantly impact long-term renal function, but the type of urinary diversion (ileal conduit or orthotopic neobladder) had no effect on renal function, and ICUD was superior in terms of long-term renal injury rate. Therefore, precise preoperative assessment and the selection of appropriate surgical approach are crucial for preserving renal function in patients with bladder cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Wang, Fang, Zhao, Chen, Zhang, Zhang, Guo and Zhang.)

To determine the pathogenicity of two different genotypes of avian hepatitis E strains in two species of birds, a total of thirty healthy 12-week-old birds were used. After inoculation, fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions were evaluated. The results revealed that CHN-GS-aHEV and CaHEV could both infect Hy-Line hens and silkie fowls, respectively. Compared to the original avian HEV strain, the cross-infected virus exhibited a delay of 2 weeks and 1 week in emerged seroconversion, viremia, fecal virus shedding, and increased ALT level, and also showed mild liver lesions. These findings suggested that CHN-GS-aHEV may have circulated in chickens. Overall, these two different genotypes of avian HEV showed some variant pathogenicity in different bird species. This study provides valuable data for further analysis of the epidemic conditions of two avian HEVs in Hy-Line hens and silkie fowls., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Machine learning is becoming a preferred method for the virtual screening of organic materials due to its cost-effectiveness over traditional computationally demanding techniques. However, the scarcity of labeled data for organic materials poses a significant challenge for training advanced machine learning models. This study showcases the potential of utilizing databases of drug-like small molecules and chemical reactions to pretrain the BERT model, enhancing its performance in the virtual screening of organic materials. By fine-tuning the BERT models with data from five virtual screening tasks, the version pretrained with the USPTO-SMILES dataset achieved R 2 scores exceeding 0.94 for three tasks and over 0.81 for two others. This performance surpasses that of models pretrained on the small molecule or organic materials databases and outperforms three traditional machine learning models trained directly on virtual screening data. The success of the USPTO-SMILES pretrained BERT model can be attributed to the diverse array of organic building blocks in the USPTO database, offering a broader exploration of the chemical space. The study further suggests that accessing a reaction database with a wider range of reactions than the USPTO could further enhance model performance. Overall, this research validates the feasibility of applying transfer learning across different chemical domains for the efficient virtual screening of organic materials.Scientific contributionThis study verifies the feasibility of applying transfer learning to large language models in different chemical fields to help organic materials perform virtual screening. Through the comparison of transfer learning from different chemical fields to a variety of organic material molecules, the high precision virtual screening of organic materials is realized., (© 2024. The Author(s).)

Objective: To detail a novel technique of robotic-assisted simple prostatectomy that makes handling the gland protruding into the bladder neck easier and can preserve the urethra and retain ejaculation function as much as possible., Patients and Methods: This is a prospective case series. Clinical data of 17 male patients who had large volume (>80 mL) benign prostatic hyperplasia (BPH) were enrolled to undergo trans-rectovesical pouch urethral-sparing robotic-assisted simple prostatectomy (usRASP). We adopted the approach through the space between the bladder neck and seminal vesicle to perform a usRASP that can avoid the detrusor skirt and fibrous matrix area of the retropubic prostate. Between the transitional zone and the peripheral zone of the large prostate, the hyperplastic prostatic gland tissue can be enucleated under direct vision while preserving the prostatic urethra and retaining the ejaculatory duct and bladder neck intact. All preoperative, perioperative and postoperative clinical data were collected, and descriptive analysis was performed., Results: The median intravesical prostatic protrusion was 19.3 mm (8.5-32.2). The median operative time was 100 min (75-140), and the median estimated blood loss was 100 mL (10-500). The median time to catheter removal was 7 days (5-7), with a median postoperative hospital stay of 2 days (2-4). After at least 6-month follow-up, the median maximum urine flow rate and postvoid residual volume were 40.1 mL/s (12.7-52.4) and 15 mL (5-23), respectively; the median International Prostate Symptom Score and Quality of Life score were 0 (0-6.3) and 1 (0-3), respectively; and the median total prostate-specific antigen was 0.84 ng/mL (0.15-1.01). All patients successfully underwent usRASP. Fifty-eight percent of patients with normal ejaculation function before surgery can still retain normal ejaculation function., Conclusion: We described a new approach to performing usRASP. This new method remarkably improved the voiding function, maintained antegrade ejaculation and did not increase the post-operative complications., Competing Interests: None of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript., (© 2024 The Author(s). BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

The significant volume change experienced by silicon (Si) anodes during lithiation/delithiation cycles often triggers mechanical-electrochemical failures, undermining their utility in high-energy-density lithium-ion batteries (LIBs). Herein, we propose a sub micro-nano-structured Si based material to address the persistent challenge of mechanic-electrochemical coupling issue during cycling. The mesoporous Si-based composite submicrospheres (M-Si/SiO 2 /CS) with a high Si/SiO 2 content of 84.6 wt.% is prepared by magnesiothermic reduction of mesoporous SiO 2 submicrospheres followed by carbon coating process. M-Si/SiO 2 /CS anode can maintain a high specific capacity of 740 mAh g -1 at 0.5 A g -1 after 100 cycles with a lower electrode thickness swelling rate of 63%, and exhibits a good long-term cycling stability of 570 mAh g -1 at 1 A g -1 after 250 cycles. This remarkable Li-storage performance can be attributed to the synergistic effects of the hierarchical structure and SiO 2 frameworks. The spherical structure mitigates stress/strain caused by the lithiation/delithiation, while the internal mesopores provide buffer space for Si expansion and obviously shorten the diffusion path for electrolyte/ions. Additionally, the amorphous SiO 2 matrix not only servers as support for structure stability, but also facilitates the rapid formation of a stable solid electrolyte interphase layer. This unique architecture offers a potential model for designing high-performance Si-based anode for LIBs., (© 2024 IOP Publishing Ltd.)

The computational method has been proven to be a promising means for pre-screening large-scale anticancer drug combinations to support precision oncology applications. Pioneering efforts have been made to develop machine learning technology for predicting drug synergy, but high computational cost for training models as well as great diversity and limited size in screening data escalate the difficulty of prediction. To address this challenge, we propose a simple machine learning framework, namely Similarity Network-based Synergy prediction (SNSynergy), for predicting synergistic effects towards new cell lines and new drug combinations by two locally weighted models CLSN and DCSN. This framework only requires a small amount of auxiliary data, like genomics information of cell lines and the molecular fingerprints or targets of drugs. Based on the assumption that similar cell lines and similar drug combinations have similar synergistic effects, CLSN and DCSN predict synergy scores through capturing individual synergy contributions of nearest cell line and drug combination neighbors, respectively. High correlations between predicted and measured synergy scores on two leading cancer cell line pharmacogenomic screening datasets (the O'Neil dataset and the NCI-ALMANAC dataset) demonstrate the effectiveness and robustness of SNSynergy. Many of the identified drug combinations are consistent with previous studies, or have been explored in clinical settings against the specific cancer type, showing that SNSynergy has the potential to supply cost-saving and effective high-throughput screening for prioritizing the most applicable cell lines and the most promising drug combinations., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Arteriovenous fistulas (AVFs) are the most common vascular access points for hemodialysis (HD), but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia (NIH). Our previous studies have revealed a highly conserved LncRNA-LncDACH1 as an important regulator of cardiomyocyte and fibroblast proliferation. Herein, we find that LncDACH1 regulates NIH in AVF in male mice with conditional knockout of smooth muscle cell-specific LncDACH1 and in male mice model of AVF with LncDACH1 overexpression by adeno-associated virus. Mechanistically, silence of LncDACH1 activates p-AKT through promoting the expression of heat shock protein 90 (HSP90) and serine/arginine-rich splicing factor protein kinase 1 (SRPK1). Moreover, LncDACH1 is transcriptionally activated by transcription factor KLF9 that binds directly to the promoter region of the LncDACH1 gene. In this work, during AVF NIH, LncDACH1 is downregulated by KLF9 and promotes NIH through the HSP90/ SRPK1/ AKT signaling axis., (© 2024. The Author(s).)

Since structural analyses and toxicity assessments have not been able to keep up with the discovery of unknown per- and polyfluoroalkyl substances (PFAS), there is an urgent need for effective categorization and grouping of PFAS. In this study, we presented PFAS-Atlas, an artificial intelligence-based platform containing a rule-based automatic classification system and a machine learning-based grouping model. Compared with previously developed classification software, the platform's classification system follows the latest Organization for Economic Co-operation and Development (OECD) definition of PFAS and reduces the number of uncategorized PFAS. In addition, the platform incorporates deep unsupervised learning models to visualize the chemical space of PFAS by clustering similar structures and linking related classes. Through real-world use cases, we demonstrate that PFAS-Atlas can rapidly screen for relationships between chemical structure and persistence, bioaccumulation, or toxicity data for PFAS. The platform can also guide the planning of the PFAS testing strategy by showing which PFAS classes urgently require further attention. Ultimately, the release of PFAS-Atlas will benefit both the PFAS research and regulation communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Postoperative pneumonia (POP) is one of the primary complications after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with postoperative mortality, extended hospital stay, and increased medical fee. Early identification of pneumonia and more aggressive treatment can improve patient outcomes. We aimed to develop a model to predict POP in aSAH patients using machine learning (ML) methods., Methods: This internal cohort study included 706 patients with aSAH undergoing intracranial aneurysm embolization or aneurysm clipping. The cohort was randomly split into a train set (80%) and a testing set (20%). Perioperative information was collected from participants to establish 6 machine learning models for predicting POP after surgical treatment. The area under the receiver operating characteristic curve (AUC), precision-recall curve were used to assess the accuracy, discriminative power, and clinical validity of the predictions. The final model was validated using an external validation set of 97 samples from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database., Results: In this study, 15.01% of patients in the training set and 12.06% in the testing set with POP after underwent surgery. Multivariate logistic regression analysis showed that mechanical ventilation time (MVT), Glasgow Coma Scale (GCS), Smoking history, albumin level, neutrophil-to-albumin Ratio (NAR), c-reactive protein (CRP)-to-albumin ratio (CAR) were independent predictors of POP. The logistic regression (LR) model presented significantly better predictive performance (AUC: 0.91) than other models and also performed well in the external validation set (AUC: 0.89)., Conclusion: A machine learning model for predicting POP in aSAH patients was successfully developed using a machine learning algorithm based on six perioperative variables, which could guide high-risk POP patients to take appropriate preventive measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhang, Wang, Ye, Zhu and Zhuge.)

Neutrophils are the most important innate immune cells in host defense against methicillin-resistant Staphylococcus aureus (MRSA). However, MRSA orchestrates precise and timely expression of a series of virulence factors, especially the chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS), to evade neutrophil-mediated host defenses. Here, we demonstrated that tripterin, a plant-derived bioactive pentacyclic triterpenoid, had a low minimum inhibitory concentration (MIC) of 1.28 µg/mL and displayed excellent anti-MRSA activity in vitro and in vivo. RNA-seq and further knockdown experiments revealed that tripterin could dramatically downregulate the expression of CHIPS by regulating the SaeRS two-component regulatory system, thereby enhancing the chemotactic response of neutrophils. Furthermore, tripterin also displayed a potential inhibitory effect on biofilm components to enhance neutrophil infiltration into the interior of the biofilm. In a mouse bacteremia model, tripterin could still maintain an excellent therapeutic effect that was significantly better than that of the traditional antibiotic vancomycin. Overall, these results suggest that tripterin possesses a superior antibacterial activity via breaking CHIPS-mediated immune evasion to promote neutrophil chemotaxis, thus providing a novel strategy for combating serious pathogenic infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To established an AI system to make the pathological diagnosis of prostate cancer., Methods: Prostate histopathological whole mount (WM) sections from patients underwent robot-assisted laparoscopic prostatectomy were prepared. All the prostate WM pathological sections were converted to digital image data and marked with different colors on the basis of the ISUP Gleason grade group. The image was then fed into a segmentation algorithm. We chose modified U-Net as our fundamental network architecture., Results: 172 patients were involved in this study. 896 pieces of prostate WM pathological sections from 160 patients, in which 826 pieces of WM sections from 148 patients were assigned to the training set randomly. After image segmentation there were totally 2,138,895 patches, of which 1,646,535 patches were valid for training. The other WM section was arranged for testing. Based on the whole image testing, AI and pathologists presented the same answers among 21 of 22 pieces of sections. To evaluate the diagnostic results at the pixel level, we anticipated correct cancer or non-cancer diagnose from this AI system. The area under the ROC curve as 96.8%. The value of pixel accuracy of three methods (binary analysis, clinically oriented analysis and analysis for different ISUP Gleason grade) were 96.93%, 95.43% and 93.88%, respectively. The value of frequency weighted IoU were 94.32%, 92.13% and 90.21%, respectively., Conclusions: This AI system is able to assist pathologists to make a final diagnosis, indicating the great potential and a wide-range of applications of AI in the medical field., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

AMG510, as the first approved inhibitor for KRAS G12C mutation, has shown promising efficacy in nonsmall-cell lung cancer and colorectal cancer harboring KRAS G12C mutation. However, the moderate response rate and the rapid emergence of acquired resistance limit the therapeutic potential of AMG510, highlighting the need for the development of combination strategies. Here, we observed the suppression of RAS-MAPK signaling induced by AMG510 was prolonged and enhanced by SOS1 knockdown. Thus, we design, synthesize, and characterize a potent and specific SOS1 degrader 23 . Compound 23 showed efficient SOS1 degradation in KRAS-driven cancer cells and achieved significant antiproliferative potency. Importantly, the combination of 23 with AMG510 suppressed RAS signaling feedback activation, showing synergistic effects against KRAS G12C mutant cells in vitro and in vivo . Our findings demonstrated that KRAS G12C inhibition plus SOS1 degradation as a potential therapeutic strategy to improve antitumor response and overcome acquired resistance to KRAS G12C inhibitor.

Tolerance to submergence-induced hypoxia is an important agronomic trait especially for crops in lowland and flooding-affected areas. Although rice ( Oryza sativa ) is considered a flood-tolerant crop, only limited cultivars display strong tolerance to prolonged submergence and/or hypoxic stress. Therefore, characterization of hypoxic resistant genes and/or germplasms have important theoretical and practical significance for rice breeding and sustained improvements. Previous investigations have demonstrated that loss-of-function of OsPIN2 , a gene encoding an auxin efflux transporter, results in the loss of root gravitropism due to disrupted auxin transport in the root tip. In this study, we revealed a novel connection between OsPIN2 and reactive oxygen species (ROS) in modulating root gravitropism and hypoxia tolerance in rice. It is shown that the OsPIN2 mutant had decreased accumulation of ROS in root tip, due to the downregulation of glycolate oxidase encoding gene OsGOX6 , one of the main H 2 O 2 sources. The morphological defects of root including waved rooting and agravitropism in OsPIN2 mutant may be rescued partly by exogenous application of H 2 O 2 . The OsPIN2 mutant exhibited increased resistance to ROS toxicity in roots due to treatment with H 2 O 2 . Furthermore, it is shown that the OsPIN2 mutant had increased tolerance to hypoxic stress accompanied by lower ROS accumulation in roots, because the hypoxia stress led to over production of ROS in the roots of the wild type but not in that of OsPIN2 mutant. Accordingly, the anoxic resistance-related gene SUB1B showed differential expression in the root of the WT and OsPIN2 mutant in response to hypoxic conditions. Notably, compared with the wild type, the OsPIN2 mutant displayed a different pattern of auxin distribution in the root under hypoxia stress. It was shown that hypoxia stress caused a significant increase in auxin distribution in the root tip of the WT but not in that of the war1 mutant. In summary, these results suggested that OsPIN2 may play a role in regulating ROS accumulation probably via mediating auxin transport and distribution in the root tip, affecting root gravitropism and hypoxic tolerance in rice seedlings. These findings may contribute to the genetic improvement and identification of potential hypoxic tolerant lines in rice.

Background: Renal fibrosis significantly contributes to the progressive loss of kidney function in chronic kidney disease (CKD), with alternatively activated M2 macrophages playing a crucial role in this progression. The serum succinate level is consistently elevated in individuals with diabetes and obesity, both of which are critical factors contributing to CKD. However, it remains unclear whether elevated succinate levels can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis., Methods: Male C57/BL6 mice were administered water supplemented with 4% succinate for 12 weeks to assess its impact on renal interstitial fibrosis. Additionally, the significance of macrophages was confirmed in vivo by using clodronate liposomes to deplete them. Furthermore, we employed RAW 264.7 and NRK-49F cells to investigate the underlying molecular mechanisms., Results: Succinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3β/β-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells., Conclusions: The causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages. Succinate-SUCNR1 played a role in activating p-Akt/p-GSK3β/β-catenin, CTGF expression, and facilitating crosstalk between macrophages and fibroblasts. Our findings suggest a promising strategy to prevent the progression of metabolic CKD by promoting the excretion of succinate in urine and/or using selective antagonists for SUCNR1., (© 2024. The Author(s).)

Covalent organic frameworks (COFs) represent an important class of crystalline porous materials with designable structures and functions. The interconnected organic monomers, featuring pre-designed symmetries and connectivities, dictate the structures of COFs, endowing them with high thermal and chemical stability, large surface area, and tunable micropores. Furthermore, by utilizing pre-functionalization or post-synthetic functionalization strategies, COFs can acquire multifunctionalities, leading to their versatile applications in gas separation/storage, catalysis, and optoelectronic devices. Our review provides a comprehensive account of the latest advancements in the principles, methods, and techniques for structural design and determination of COFs. These cutting-edge approaches enable the rational design and precise elucidation of COF structures, addressing fundamental physicochemical challenges associated with host-guest interactions, topological transformations, network interpenetration, and defect-mediated catalysis.

Background: Lung cancer is one of the most common and deadly cancers in humans. P73 , a member of the p53 family, is a vital gene for the carcinogenesis of lung cancer. Single nucleotide polymorphism (SNP) of P73 gene may affect the risk of lung cancer. Therefore, we performed a meta-analysis of p73 SNP and lung cancer risk using the most recent data., Methods: A total of 1407 articles from EMBASE, Web of science, PubMed and Chinese National Knowledge Infrastructure (CNKI) databases were identified initially from the search. A meta-analysis of the association between P73 polymorphism and lung cancer risk was performed based on various genetic models and by type of lung cancer and race., Results: Seven articles published in either English or Chinese with English abstract were eventually selected for final analysis. The total pooled population included 6214 subjects (2,897 cases and 3,317 controls). The results showed that p73 RS2273953 to RS1801173 polymorphism was associated with increased risk of lung cancer in Caucasians but not in Asians. Within Asians, those with p73 GC/GC may have an increased risk for squamous carcinoma compared to those with GC/AT+AT/AT polymorphism., Conclusions: Our analysis suggested a lack of association between p73 RS2273953 to RS1801173 polymorphism and risk of lung cancer overall. However, patients with GC/GC polymorphism showed an increased risk for squamous carcinoma in the lung compared to those with GC/AT+AT/AT in Asians., Competing Interests: None., (IJCEP Copyright © 2023.)

The status of draining lymph nodes (LNs) is critical for determining the treatment and prognosis of cancer that spreads through the lymphatic system. Indocyanine green (ICG) fluorescence imaging has been widely used in sentinel LN (SLN) biopsy technology and has shown favorable effects. However, this too has its own limitations, such as fluorescence instability and diffusion imaging. In this study, we developed macrophage cell membrane-camouflaged ICG-loaded biomimetic nanoparticles (M@F127-ICG) for accurate SLN imaging. ICG selectively positioned at the hydrophobic-hydrophilic interfaces of pluronic F127 micelles protected itself from quenching in aqueous solution, thereby maintaining fluorescence stability and improving fluorescence intensity. In addition, to further improve the aggregation in SLN, the micellar surface was coated with a layer of biomimetic macrophage cell membrane to target LN-resident macrophages. In vivo fluorescence imaging demonstrated that M@F127-ICG significantly enhanced the fluorescence signal and improved the imaging efficiency of SLN. Thus, selectively positioning ICG in the biomimetic nanoplatform enhanced the fluorescence intensity and stability, providing a novel tracer for timely and accurate SLN imaging.

Potassium-based energy storage has emerged as a promising alternative for advanced energy storage systems, driven by the abundance of potassium, fast ion migration, and low standard electrode potential. Hybrid capacitors, which combine the desirable characteristics of batteries and supercapacitors, offer a compelling solution for efficient energy storage. In this study, we present the development of versatile composite materials, specifically potassium vanadium fluorophosphate (KVPO 4 F) composites, utilizing a sol-gel method. These composites enable tunable potassium storage and charge transport kinetics within regulated voltage windows, serving as both cathode and anode materials. The anode composite, composed of KVPO 4 F and hierarchical porous carbon (HPC), exhibited exceptional stability over 400 cycles within a low-voltage window. On the other hand, the cathode composite, consisting of battery-like KVPO 4 F and physisorption activated carbon (AC), demonstrated great potential as a cathode material, striking a balance between specific energy and cycle life within a regulated high-voltage window. By integrating KVPO 4 F/C as the anode and KVPO 4 F/AC as the cathode, we successfully created potassium-ion hybrid capacitors (PIHCs) that showcased an impressive capacity retention of 83% after 10,000 cycles within a high voltage window of 0.5-4.3 V. Furthermore, to explore the application of these materials in miniaturized energy storage, we fabricated potassium-ion micro hybrid capacitors (PIMHCs) with interdigitated electrodes. These devices exhibited a high areal energy density of 18.8 μWh cm -2 at a power density of 111.6 μW cm -2 , indicating their potential for compact energy storage systems. The results of this study demonstrate the versatility and efficacy of the developed KVPO4F composite materials, highlighting their potential for future advancements in potassium-based energy storage technologies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prime editing (PE) is a versatile CRISPR-Cas based precise genome-editing platform widely used to introduce a range of possible base conversions in various organisms. However, no PE systems have been shown to induce heritable mutations in tobacco, nor in any other dicot. In this study, we generated an efficient PE system in tobacco that not only introduced heritable mutations, but also enabled anthocyanin-based reporter selection of transgene-free T 1 plants. This system was used to confer Z-abienol biosynthesis in the allotetraploid tobacco cultivar HHDJY by restoring a G>T conversion in the NtCPS2 gene. High levels of Z-abienol were detected in the leaves of homozygous T 1 plants at two weeks after topping. This study describes an advance in PE systems and expands genome-editing toolbox in tobacco, even in dicots, for use in basic research and molecular breeding. And restoring biosynthesis of Z-abienol in tobacco might provide an efficient way to obtain Z-abienol in plants., (© 2023. Science China Press.)

As a naturally occurring cytolytic peptide, melittin (MLT) not only exhibits a potent direct tumor cell-killing effect but also possesses various immunomodulatory functions. MLT shows minimal chances for developing resistance and has been recognized as a promising broad-spectrum antitumor drug because of this unique dual mechanism of action. However, MLT still displays obvious toxic side effects during treatment, such as nonspecific cytolytic activity, hemolytic toxicity, coagulation disorders, and allergic reactions, seriously hampering its broad clinical applications. With thorough research on antitumor mechanisms and the rapid development of nanotechnology, significant effort has been devoted to shielding against toxicity and achieving tumor-directed drug delivery to improve the therapeutic efficacy of MLT. Herein, we mainly summarize the potential antitumor mechanisms of MLT and recent progress in the targeted delivery strategies for tumor therapy, such as passive targeting, active targeting and stimulus-responsive targeting. Additionally, we also highlight the prospects and challenges of realizing the full potential of MLT in the field of tumor therapy. By exploring the antitumor molecular mechanisms and delivery strategies of MLT, this comprehensive review may inspire new ideas for tumor multimechanism synergistic therapy., (© 2023. The Author(s).)

This article presents a self-corrective network-based long-term tracker (SCLT) including a self-modulated tracking reliability evaluator (STRE) and a self-adjusting proposal postprocessor (SPPP). The targets in the long-term sequences often suffer from severe appearance variations. Existing long-term trackers often online update their models to adapt the variations, but the inaccurate tracking results introduce cumulative error into the updated model that may cause severe drift issue. To this end, a robust long-term tracker should have the self-corrective capability that can judge whether the tracking result is reliable or not, and then it is able to recapture the target when severe drift happens caused by serious challenges (e.g., full occlusion and out-of-view). To address the first issue, the STRE designs an effective tracking reliability classifier that is built on a modulation subnetwork. The classifier is trained using the samples with pseudo labels generated by an adaptive self-labeling strategy. The adaptive self-labeling can automatically label the hard negative samples that are often neglected in existing trackers according to the statistical characteristics of target state, and the network modulation mechanism can guide the backbone network to learn more discriminative features without extra training data. To address the second issue, after the STRE has been triggered, the SPPP follows it with a dynamic NMS to recapture the target in time and accurately. In addition, the STRE and the SPPP demonstrate good transportability ability, and their performance is improved when combined with multiple baselines. Compared to the commonly used greedy NMS, the proposed dynamic NMS leverages an adaptive strategy to effectively handle the different conditions of in view and out of view, thereby being able to select the most probable object box that is essential to accurately online update the basic tracker. Extensive evaluations on four large-scale and challenging benchmark datasets including VOT2021LT, OxUvALT, TLP, and LaSOT demonstrate superiority of the proposed SCLT to a variety of state-of-the-art long-term trackers in terms of all measures. Source codes and demos can be found at https://github.com/TJUT-CV/SCLT.

Tetracycline (TC) is a commonly used antibiotic that affects various physiological processes in plants. However, its negative effects on plants remain poorly understood at the molecular level. To ascertain the TC toxicity in the roots, transcriptomic, cytological, and physiological analyses were performed to explore the molecular mechanisms of TC influencing the growth of hulless barley root. At a low concentration (1 mg/L), TC promoted root growth by upregulating the genes related to the flavonoid pathway. At high concentrations (10, 100, and 200 mg/L), TC downregulated genes related to homologous recombination in the root meristem zone and inhibited the mitosis index by 16.4%. Disruption of the DNA repair process can lead to chromosomal aberrations, resulting in a 6.8% C-mitosis rate in the most severe cases. Finally, root growth was inhibited by TC, as evidenced by a reduction in root viability, an increase in reactive oxygen species content, and an inhibition of root length. Cross-comparison of physiological and cytological characterizations and transcriptomic information revealed changes in genetic processes under TC stress. Overall, we present an early genetic strategy to study the significant influence of TC stress on roots., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Although studies have shown severe Coronavirus disease 2019 (COVID-19) outcomes in patients with pre-existing coronary heart disease (CHD), the prognosis of COVID-19 patients with pre-existing CHD remains uncertain primarily due to the limited number of patients in existing studies. This study aimed to investigate the impacts of pre-existing CHD on the prognosis of COVID-19 patients. Five electronic databases were searched for eligible studies. This article focused on cohort and case-control studies involving the prognosis of COVID-19 patients with pre-existing CHD. The meta-analysis was performed using a random effects model. The odds ratios (ORs) and 95% confidence intervals (CIs) were used as valid indicators. The study was registered in PROSPERO with the identifier: CRD42022352853. A total of 81 studies, involving 157,439 COVID-19 patients, were included. The results showed that COVID-19 patients with pre-existing CHD exhibited an elevated risk of mortality (OR = 2.45; 95%CI: [2.04, 2.94], P < 0.001), severe/critical COVID-19 (OR = 2.57; 95%CI: [1.98, 3.33], P < 0.001), Intensive Care Unit or Coronary Care Unit (ICU/CCU) admission: (OR = 2.75, 95%CI: [1.61, 4.72], P = 0.002), and reduced odds of discharge/recovery (OR = 0.43, 95%CI: [0.28, 0.66], P < 0.001) compared to COVID-19 patients without pre-existing CHD. Subgroup analyses indicated that the prognosis of COVID-19 patients with pre-existing CHD was influenced by publication year, follow-up duration, gender, and hypertension. In conclusion, pre-existing CHD significantly increases the risk of poor prognosis in patients with COVID-19, particularly in those male or hypertensive patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Postoperative pneumonia (POP) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) associated with increased mortality rates, prolonged hospitalization, and high medical costs. It is currently understood that identifying pneumonia early and implementing aggressive treatment can significantly improve patients' outcomes. The primary objective of this study was to explore risk factors and develop a logistic regression model that assesses the risks of POP., Methods: An internal cohort of 613 inpatients with aSAH who underwent surgery at the Neurosurgical Department of First Affiliated Hospital of Wenzhou Medical University was retrospectively analyzed to develop a nomogram for predicting POP. We assessed the discriminative power, accuracy, and clinical validity of the predictions by using the area under the receiver operating characteristic curve (AUC), the calibration curve, and decision curve analysis (DCA). The final model was validated using an external validation set of 97 samples from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database., Results: Among patients in our internal cohort, 15.66% ( n = 96/613) of patients had POP. The least absolute shrinkage and selection operator (LASSO) regression analysis identified the Glasgow Coma Scale (GCS), mechanical ventilation time (MVT), albumin, C-reactive protein (CRP), smoking, and delayed cerebral ischemia (DCI) as potential predictors of POP. We then used multivariable logistic regression analysis to evaluate the effects of these predictors and create a final model. Eighty percentage of patients in the internal cohort were randomly assigned to the training set for model development, while the remaining 20% of patients were allocated to the internal validation set. The AUC values for the training, internal, and external validation sets were 0.914, 0.856, and 0.851, and the corresponding Brier scores were 0.084, 0.098, and 0.143, respectively., Conclusion: We found that GCS, MVT, albumin, CRP, smoking, and DCI are independent predictors for the development of POP in patients with aSAH. Overall, our nomogram represents a reliable and convenient approach to predict POP in the patient population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin, Wang, Zhang, Yang, Lou, Xu and Cai.)

Purpose: Retinal pigment epithelium (RPE) dysfunction induced by oxidative stress-related epithelial-mesenchymal transition (EMT) of RPE is the primary underlying mechanism of age-related macular degeneration (AMD). Kallistatin (KAL) is a secreted protein with an antioxidative stress effect. However, the relationship between KAL and EMT in RPE has not been determined. Therefore we aimed to explore the impact and mechanism of KAL in oxidative stress-induced EMT of RPE., Methods: Sodium iodate (SI) was injected intraperitoneally to construct the AMD rat model and investigate the changes in RPE morphology and KAL expression. KAL knockout rats and KAL transgenic mice were used to explain the effects of KAL on EMT and oxidative stress. In addition, Snail overexpressed adenovirus and si-RNA transfected ARPE19 cells to verify the involvement of Snail in mediating KAL-suppressed EMT of RPE., Results: AMD rats induced by SI expressed less KAL in the retina, and KAL knockout rats showed RPE dysfunction spontaneously where EMT and reactive oxygen species (ROS) production increased in RPE. In contrast, KAL overexpression attenuated EMT and ROS levels in RPE, even in TGF-β treatment. Mechanistically, Snail reversed the beneficial effect of KAL on EMT and ROS reduction. Moreover, KAL ameliorated SI-induced AMD-like pathological changes., Conclusions: Our findings demonstrated that KAL inhibits oxidative stress-induced EMT by downregulating the transcription factor Snail. Herein, KAL knockout rats may be an appropriate animal model for observing spontaneous RPE dysfunction for AMD-like retinopathy, and KAL may represent a novel therapeutic target for treating dry AMD.

Problem: Virtual reality technology has been used to treat amblyopia in children. However, it is unclear how virtual reality technology differs from conventional patching therapy in terms of effectiveness., Eligibility Criteria: Eligible randomized controlled studies were retrieved from PubMed, Embase, Scopus, the Cochrane Library, and Web of Science through February 2023., Sample: Eight studies included 10 trials with 459 participants were included in the current meta-analysis. Two studies (Herbison et al., 2016; Huang et al., 2022) included two trials each. Thus, a total of ten trials were included in the current meta-analysis., Results: Overall, virtual reality technology treatment significantly improved visual acuity by 0.07 log MAR (95% confidence interval [CI], -0.11 to -0.02; P < 0.001; I 2  = 94.4%) compared with traditional patching therapy. In addition, subgroup analyses also revealed that treatment with virtual reality technology was more effective when the child was younger than seven years old, or when the duration of the intervention was no more than twenty hours., Conclusions: Virtual reality technology treatment showed significant effects in improving visual acuity in children who were seven years of age or younger with amblyopia., Implications: Virtual reality technology treatment is effective in treating amblyopia in children. Virtual reality therapy is also entertaining and popular among children and can be applied to the treatment of amblyopia in children in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The capillary force is critical to the moving and breaking of droplets on fibers. This study brings forward a 3-D model reconstruction method for a clam-shell droplet on fibers and obtains the capillary force by the surface integral of Laplace pressure on the whole droplet. The capillary force results are verified by the droplet gravity and axial drag force, respectively. Moreover, the tensile tangential stresses are analyzed to illustrate the top limits of Laplace pressure against droplet breaking or sliding on the fiber. The experiment shows that the capillary force obtained by the 3-D model accurately describes the vertical and tangential forces of the clam-shell droplet on the fiber. Sharp shrinking of the cross-section on the droplet's upper part results in an exponential increase in tensile and tangential stresses, which makes the droplet break or move on the fiber.

Background: Lower extremity deep vein thrombosis (DVT) is one of the major postoperative complications in patients with ruptured intracranial aneurysms (RIA) who underwent endovascular treatment (EVT). However, patient-specific predictive models are still lacking. This study aimed to construct and validate a nomogram model for estimating the risk of lower extremity DVT for RIA patients who underwent EVT., Methods: This cohort study enrolled 471 RIA patients who received EVT in our institution between 1 January 2020 to 4 February 2022. Perioperative information on participants is collected to develop and validate a nomogram for predicting lower extremity DVT in RIA patients after EVT. Predictive accuracy, discriminatory capability, and clinical effectiveness were evaluated by concordance index (C-index), calibration curves, and decision curve analysis., Result: Multivariate logistic regression analysis showed that age, albumin, D-dimer, GCS score, middle cerebral artery aneurysm, and delayed cerebral ischemia were independent predictors for lower extremity DVT. The nomogram for assessing individual risk of lower extremity DVT indicated good predictive accuracy in the primary cohort (c-index, 0.92) and the validation cohort (c-index, 0.85), with a wide threshold probability range (4-82%) and superior net benefit., Conclusion: The present study provided a reliable and convenient nomogram model developed with six optimal predictors to assess postoperative lower extremity DVT in RIA patients, which may benefit to strengthen the awareness of lower extremity DVT control and supply appropriate resources to forecast patients at high risk of RIA-related lower extremity DVT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhu, Zhang, Yuan, Wang, Ye, Jiang and Ye.)

Shallow geothermal energy reserves are abundant and widely distributed in Shandong Province. Vigorously developing and utilizing shallow geothermal energy will play a significant role in improving energy pressure in Shandong Province. The energy efficiency of ground source heat pumps is closely related to geological and other conditions. However, few studies on geothermal exploitation and utilization have been affected by economic policies. This article will investigate the operation of shallow geothermal engineering in Shandong Province, summarize the current number of operating projects, calculate the engineering annual comprehensive performance coefficient (ACOP), analyze the size characteristics of different cities, and analyze their correlation with economy and policy. Through research, it is found that the number of shallow geothermal energy development and utilization is significantly positively correlated with socioeconomic level and policy orientation, and has a relatively small relationship with ACOP. The research results provide a basis and suggestions for improving and optimizing the energy efficiency coefficient of geothermal heat pumps and promoting the development and utilization of shallow geothermal., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Porphyrin-based MOFs combine the unique photophysical and electrochemical properties of metalloporphyrins with the catalytic efficiency of MOF materials, making them an important candidate for light energy harvesting and conversion. However, accurate prediction of the band gap of porphyrin-based MOFs is hampered by their complex structure-function relationships. Although machine learning (ML) has performed well in predicting the properties of MOFs with large training datasets, such ML applications become challenging when the training data size of the materials is small. In this study, we first constructed a dataset of 202 porphyrin-based MOFs using DFT computations and increased the training data size using two data augmentation strategies. After that, four state-of-the-art neural network models were pre-trained with the recognized open-source database QMOF and fine-tuned with our augmented self-curated datasets. The GCN models predicted the band gaps of the porphyrin-based materials with the lowest RMSE of 0.2767 eV and MAE of 0.1463 eV. In addition, the data augmentation strategy rotation and mirroring effectively decreased the RMSE by 38.51% and MAE by 50.05%. This study demonstrates that, when proper transfer learning and data augmentation strategies are applied, machine learning models can predict the properties of MOFs using small training data., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

This investigation is motivated by interest in nanostructured FeOOH anodes for aqueous asymmetric supercapacitors operating in Na 2 SO 4 electrolyte. The research goal is the fabrication of anodes with high active mass loading of 40 mg cm -2 , high capacitance and low resistance. The influence of high-energy ball milling (HEBM), capping agents and alkalizer on the nanostructure and capacitive properties is investigated. HEBM promotes the crystallization of FeOOH, which results in capacitance reduction. Capping agents from the catechol family, such as tetrahydroxy-1,4-benzoquinone (THB) and gallocyanine (GC), facilitate the fabrication of FeOOH nanoparticles, eliminate the formation of micron size particles and allow the fabrication of anodes with enhanced capacitance. The analysis of testing results provided insight into the influence of the chemical structure of the capping agents on nanoparticle synthesis and dispersion. The feasibility of a conceptually new strategy for the synthesis of FeOOH nanoparticles is demonstrated, which is based on the use of polyethylenimine as an organic alkalizer-dispersant. The capacitances of materials prepared using different nanotechnology strategies are compared. The highest capacitance of 6.54 F cm -2 is obtained using GC as a capping agent. The obtained electrodes are promising for applications as anodes for asymmetric supercapacitors.

TiO 2 is considered as a low cost, long-term stable, and safe anode for high power K-ion hybrid capacitors (KICs) due to its abundant reserve, small volume expansion rate, and sloping voltage plateau that avoids K-ion plating at high voltage polarization. However, the enhancement of its low capacity and sluggish kinetics caused by poor electroconductivity and high insertion barrier is still challenging to further develop high-performance KICs. Herein, the reduced graphene oxide (rGO) is embedded in the walls of 3D ordered macro-/mesoporous TiO 2 (termed as TiO 2 @rGO framework) to create intimate TiO 2 /rGO interfaces, ensuring the effectively electron transportation during potassiation/depotassiation of TiO 2 while maintaining rapid ions/electrolyte diffusion. Furthermore, the controlled amorphous TiO 2 framework can further lower the lattice insertion energies, contributing to a fast accommodation of K-ion. As expected, the amorphous TiO 2 @rGO framework (TiO 2 @rGO-1) exhibits a superior rate capability (148.8 mAh g -1 at 5 A g -1 ) and cycling stability (171.2 mAh g -1 at 1 A g -1 after 800 cycles). The assembled KICs can reach a high energy/power density of 125.2 Wh kg -1 /4267.4 W kg -1 as well as a long-term lifespan. This tactic provides a reliable and general way to design a TiO 2 -based anode with fast kinetics toward high-performance KICs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Androgen deprivation in cases of castration-resistant prostate cancer (CRPC) leads to adverse effects, including loss of muscle and bone mass and gain of subcutaneous fat. The tumor-specific suppression of androgen receptor (AR) signaling, while not global, may reduce side effects. We present a class of small-molecular conjugates consisting of an AR antagonist linked to a heat shock protein 90 (Hsp90) inhibitor. We demonstrate that the high accumulation of Hsp90 on the surface of CRPC cells allows uptake of conjugates and increases the enrichment of drugs in the tumor cells. After penetrating prostate cancer cells, the conjugates not only inhibit AR function by the antagonist component but also bind to Hsp90 and suppress the AR protein level. Compared to AR antagonists, these conjugates showed improved tumor-targeting ability and enhanced potency against Enzalutamide-resistant 22Rv1 cells.

Machine learning (ML) models have received increasing attention as a new approach for the virtual screening of organic materials. Although some ML models trained on large databases have achieved high prediction accuracy, the application of ML to certain types of organic materials is limited by the small amount of available data. On the other hand, metalloporphyrins and porphyrins (MpPs) have received increasing attention as potential photocatalysts, and recent studies have found that both HOMO/LUMO energy levels and energy gaps are important factors controlling the MpP photocatalysts. Since the training data of MpPs are insufficient and limited to porphyrin-based dyes, in this study, we proposed a deep transfer learning approach to rapidly predict the HOMO/LUMO energy levels and energy gaps of MpPs. To complement the open-source Porphyrin-based Dyes Database (PBDD), we curated a new database, the Metalloporphyrins and Porphyrins Database (MpPD), in which MpPs were specifically designed as potential photocatalysts and the HOMO/LUMO energies were calculated by advanced DFT functionals. We proposed PorphyBERT, a BERT-based regression model that was pre-trained with PBDD and fine-tuned with MpPD. The model performed satisfactorily in predicting HOMO and LUMO energies and energy gap with RMSEs of 0.0955, 0.0988, and 0.0787 eV and MAEs of 0.0774, 0.0824, and 0.0549 eV. Furthermore, due to its unique unsupervised pre-training phase, the model is not affected by the difference in computational functionals between pre-training and fine-tuning databases. Finally, we recommended 12 MpPs as potential photocatalysts for CO 2 reduction with out-of-sample model predictions of energy gaps close to the values calculated by DFT.

Background: Bedtime procrastination (BP), a special type of health behavior procrastination, is considered to be a failure of self-control. Notably, self-control may mediate the effect of trait anxiety on general procrastination. However, there is no evidence demonstrating the role of self-control in the relationship between trait anxiety and BP. Moreover, the association between BP and trait anxiety has not yet been thoroughly studied. Therefore, the present study aimed to explore the direct relationship between them as well as the mediating role of self-control in this relationship., Methods: This cross-sectional survey included 718 college students enrolled in Chinese universities between October 2018 and January 2020. The Chinese versions of the Bedtime Procrastination Scale, the Self-Control Scale, and the Trait Anxiety Inventory were used to evaluate BP, self-control, and trait anxiety, respectively., Results: Multiple linear regression analysis revealed trait anxiety independently predicted BP while controlling for demographic characteristics. Correlation analyses showed that BP was positively correlated with trait anxiety, but negatively related to self-control. Structural equation modeling further revealed a mediating role of self-control in the relationship between trait anxiety and BP., Conclusions: Trait anxiety is a significant independent predictor of BP and may induce BP directly or indirectly through the effect of self-control. These findings provide a deeper understanding of the relationship between trait anxiety and BP and the underlying mechanism by exploring the mediating effect of self-control. As such, trait anxiety and self-control should be included in prevention and intervention strategies to address BP behavior in college students., (© 2022. International Society of Behavioral Medicine.)

Multiple myeloma (MM) is the second most common hematological malignancy with poor prognosis. Enhancer of zeste homolog 2 (EZH2) is the enzymatic subunit of polycomb repressive complex 2 (PRC2), which catalyzes trimethylation of histone H3 lysine 27 (H3K27me3) for transcriptional repression. EZH2 have been implicated in numerous hematological malignancies, including MM. However, noncanonical functions of EZH2 in MM tumorigenesis are not well understood. Here, we uncovered a noncanonical function of EZH2 in MM malignancy. In addition to the PRC2-mediated and H3K27me3-dependent canonical function, EZH2 interacts with cMyc and co-localizes with gene activation-related markers, promoting MM tumorigenesis in a PRC2- and H3K27me3-independent manner. Both canonical EZH2-PRC2 and noncanonical EZH2-cMyc complexes can be effectively depleted in MM cells by MS177, an EZH2 degrader we reported previously, leading to profound activation of EZH2-PRC2-associated genes and simultaneous suppression of EZH2-cMyc oncogenic nodes. The MS177-induced degradation of both canonical EZH2-PRC2 and noncanonical EZH2-cMyc complexes also reactivated immune response genes in MM cells. Phenotypically, targeting of EZH2's both canonical and noncanonical functions by MS177 effectively suppressed the proliferation of MM cells both in vitro and in vivo. Collectively, this study uncovers a new noncanonical function of EZH2 in MM tumorigenesis and provides a novel therapeutic strategy, pharmacological degradation of EZH2, for treating EZH2-dependent MM., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Rationale: Laryngeal obstruction is a life-threatening adverse event that requires urgent and appropriate management, particularly in patients with coexisting cardiopulmonary and brain comorbidities. However, laryngeal obstruction caused by laryngeal neuroendocrine tumors has rarely been reported., Patient Concerns: Neuroendocrine tumors can cause pathological changes in the neuro-humoral system, and asphyxia caused by airway obstruction has a more adverse effect on patients with neuroendocrine tumors., Diagnoses: We report the case of a 64-year-old man with clinical manifestations of dyspnea. Preoperative and intraoperative pathological examination indicated that the patient was diagnosed with life-threatening airway obstruction caused by a laryngeal neuroendocrine tumor, pneumonia, and scoliosis., Interventions: The patient underwent laryngeal tumor resection under general anesthesia. He was recovered well and was generally good without the necessity of undergoing radiotherapy and chemotherapy at the 6-months follow-up., Outcomes: This case report has provided an emergency treatment strategy associated with awake intubation. We concluded that flexible establishment of an artificial airway, skilled anesthesia and surgical manipulation, and necessary postoperative intensive care are extremely important for improving the prognosis of patients with severely difficult airway. It is noteworthy that the timely adjust for endotracheal intubation strategy according to the patient's response is needed. It is important for the long-term prognosis of patients to avoid the establishment of a traumatic artificial airway and the occurrence of adverse complications., Lessons: 1. Introduction; 2. Case presentation; 3. Discussion; 4. Conclusion., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The erector spinae plane (ESP) block is a newly defined regional anesthesia technique first described in 2016. The aim of this meta-analysis is to assess the efficacy of ESP block in improving analgesia following lumbar surgery., Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) that compared the analgesic efficacy of the ESP block with non-block care for lumbar surgery from inception 3 August 2021. The primary outcomes were postoperative opioid consumption and pain scores during the first 24 h. Postoperative pain was measured as pain at rest and on movement at postoperative 0, 4, 8, 12, and 24 h expressed on a visual analog scale (VAS), where 0 = no pain and 10 = the most severe pain., Results: 11 studies involving 775 patients were included in our analysis. The use of ESP block significantly decreased 24-h opioid consumption (WMD, -8.70; 95% CI, -10.48 to -6.93; I 2  = 97.5%; P < 0.001) compared with the non-block. Moreover, ESP block reduced pain scores at postoperative time-points up to 24 h. ESP block also prolonged the time to first analgesic request (WMD = 6.93; 95% CI: 3.44 to 10.43, I 2  = 99.8%; P < 0.001). There was less PONV with ESP block versus non-block group (RR, 0.354; 95% CI, 0.23 to 0.56; I 2  = 25.2%; P < 0.001), but no difference in pruritus., Conclusions: ESP block provides less opioid consumption and PONV, lower pain scores, and longer time to first analgesic request in patients undergoing lumbar surgery compared to general anesthesia alone., (© 2023. The Author(s).)

Two-dimensional (2D) layered MoSe 2 has been demonstrated to be a promising electrode material for new energy storage systems. However, its nature of poor conductivity and the undesirable interlayer spacing hinder its further application. In this paper, a general and simple plasma-enhanced chemical vapor deposition method is proposed to produce 2D heterolayer-structured MoSe 2 -carbon (MoSe 2 /C) with carbon atoms inserted in the MoSe 2 layers. After morphology optimization, when applying flat-type MoSe 2 /C-200 nanosheets with an enlarged interlayer spacing of 0.79 nm as the anode and activated carbon as the cathode, the assembled sodium-ion hybrid capacitors can reach a maximum energy/power density of 116.5 W h kg -1 /107.5 W kg -1 and exhibit superior cycling durability (91.3% capacitance retention after 4000 cycles at 1 A g -1 ). The good electrochemical property can be ascribed to the enlarged interlayer spacing that can offer fast diffusion channels for Na ions, and the carbon layer sandwiched in the MoSe 2 layer can not only enhance the electron transfer, accelerating the reaction kinetics, but also alleviate the volume change of MoSe 2 , ensuring the good stability of the electrode. The proposed approach can also be extended to other 2D transition metal chalcogenide (TMC) materials for constructing the TMC/C heterostructures for the application in energy storage systems.

Geothermal energy is new, environmentally friendly, and clean energy, which is of great significance to realize energy saving and emission reduction. The study of the genesis mechanism of geothermal water is the key to its rational development and utilization. In this study, based on 14 sets of water samples from the eastern section of the copper well mining area of Yinan Gold Mine, mineral saturation index, isotope analysis (δ 18 O, δD), Si-enthalpy mixing equation, and geochemical geothermal temperature scale were used to analyze the thermal storage temperature, recharge characteristics, mixing ratio, circulation depth, and fluid passage to reveal the geothermal water fugitive transmission pattern and genesis mechanism in the study area and to propose a geothermal water genesis model. The study shows that the water supply elevation in the area is between 687.22 and 1164.15 m and a large amount of cold water recharged it. It is inferred that the recharge area is the precipitation in the Northwest Mountain range and surrounding atmosphere. Groundwater flows along the fracture zone in a south-easterly direction. It receives heating from the surrounding rocks, where the water level rises at the fracture zone intersection and is stored in the lower and middle Cambrian thermal reservoirs and continues to receive heating from deeper heat sources. Based on this study and previous regional research data, the fault structure in this area is within the influence range of the energy field of the Yishu fault zone. Yishu fault zone becomes the heating source under the background of cold water. It is inferred that the east-east Yishu fault zone in the study area may also be the recharge area., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The yield and quality of tomatoes (Solanum lycopersicum) is seriously affected by Phytophthora infestans. The long non-coding RNA (lncRNA) Sl-lncRNA39896 is induced after P. infestans infection and was previously predicted to act as an endogenous target mimic (eTM) for the microRNA Sl-miR166b, which function in stress responses. Here, we further examined the role of Sl-lncRNA39896 and Sl-miR166b in tomato resistance to P. infestans. Sl-miR166b levels were higher in Sl-lncRNA39896-knockout mutants than in wild-type plants, and the mutants displayed enhanced resistance to P. infestans. A six-point mutation in the region of Sl-lncRNA39896 that binds to Sl-miR166b disabled the interaction, suggesting that Sl-lncRNA39896 acts as an eTM for Sl-miR166b. Overexpressing Sl-miR166b yielded a similar phenotype to that produced by Sl-lncRNA39896-knockout, whereas silencing of Sl-miR166b impaired resistance. We verified that Sl-miR166b cleaved transcripts of its target class III homeodomain-leucine zipper genes SlHDZ34 and SlHDZ45. Silencing of SlHDZ34/45 decreased pathogen accumulation in plants infected with P. infestans. Additionally, jasmonic acid and ethylene contents were elevated following infection in the plants with enhanced resistance. Sl-lncRNA39896 is the first known lncRNA to negatively regulate resistance to P. infestans in tomato. We propose a novel mechanism in which the lncRNA39896-miR166b-HDZ module modulates resistance to P. infestans., (© 2022 Institute of Botany, Chinese Academy of Sciences.)

The oil development has been oriented toward deep-layer reservoirs and the commingling production and the separate-layer fracturing are important development methods. Currently, limited attention is given to the pressure transient analysis (PTA) of the fractured wells located in a stratified reservoir. Moreover, the proppant is very difficult to move inside the hydraulic fracture in the deep-layer reservoir, leading to the uneven fracture conductivity along the hydraulic fracture and increasing the complexity of PTA. To fill this gap, this work presented a fully analytical well test model for hydraulically fractured wells with changing fracture conductivity in stratified reservoirs, which is convenient to be used for interpreting the recorded pressure data from the oilfield due to its analytical nature. The establishment of this model is based on the trilinear flow model, Duhamel theorem, and pressure superposition principle. A systematic verification is conducted to ensure the validity of the proposed model. Furthermore, we offer a sensitivity analysis to investigate the effect of crucial parameters on pressure and pressure derivative, including the fracture extension, fracture conductivity, transmissibility factor, and storativity factor. Finally, a field case of a four-layer fractured well from Xinjiang Oilfield in Junggar Basin is interpreted to demonstrate the practicability of the presented model., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Aims: This study is designed to explore the effect of compound Danshen injection combined with magnesium sulfate on TNF- α , NO, oxidative stress, and therapeutic efficacy in severe preeclampsia (S-PE)., Methods: Sixty S-PE patients were placed into the control group and the therapy group, randomly. The control group was under the treatment of magnesium sulfate, and the therapy group was under the treatment of compound Danshen injection with magnesium sulfate. After treatment, the therapeutic efficacy of the two groups was comparatively analyzed., Results: 7 days after treatment, DBP, SBP, and 24 h urinary protein were sharply lower than those before treatment. The 24 h urinary protein was notably lower in the therapy group. After treatment, the expression level of TNF- α in both groups was notably higher than before treatment, while NO level was higher than that before treatment. Furthermore, D-D level in two groups was dramatically decreased compared to that before treatment. Moreover, Fib, PT, and APTT in two groups showed statistically significant differences after 7 days. The contents of ALT, AST, BUN, and Scr in therapy group were notably lower than those in control group., Conclusion: Our results indicated that compound Danshen injection could improve renal function, blood hypercoagulability, and oxidative stress level and had a better therapeutic effect on S-PE., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yanling Zhou et al.)

Serotonin receptors are important targets for established therapeutics and drug development as they are expressed throughout the human body and play key roles in cell signaling. There are 12 serotonergic G protein-coupled receptor members encoded in the human genome, of which the 5-hydroxytryptamine (5-HT) 5A receptor (5-HT 5A R) is the least understood and lacks selective tool compounds. Here, we report four high-resolution (2.73-2.80 Å) structures of human 5-HT 5A Rs, including an inactive state structure bound to an antagonist AS2674723 by crystallization and active state structures bound to a partial agonist lisuride and two full agonists, 5-carboxamidotryptamine (5-CT) and methylergometrine, by cryo-EM. Leveraging the new structures, we developed a highly selective and potent antagonist for 5-HT 5A R. Collectively, these findings both enhance our understanding of this enigmatic receptor and provide a roadmap for structure-based drug discovery for 5-HT 5A R., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Enhancer of zeste homolog 2 (EZH2), a catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed in triple-negative breast cancer (TNBC), correlating with poor prognosis. However, EZH2 catalytic inhibitors are ineffective in suppressing the growth of TNBC cells that are dependent on EZH2. Knockdown of EZH2 inhibits the proliferation of these cells, suggesting that EZH2 protein overexpression but not its catalytic activity is critical for driving TNBC progression. Several proteolysis targeting chimera (PROTAC) degraders of EZH2, including the von Hippel-Lindau (VHL)-recruiting PROTAC YM281, have been reported. However, the effects of these EZH2 PROTACs in TNBC cells were not investigated. Here, we report the discovery and characterization of a novel, potent, and selective EZH2 PROTAC degrader, MS8815 (compound 16 ), which induced robust EZH2 degradation in a concentration-, time-, and proteasome-dependent manner in TNBC cells. Importantly, 16 effectively suppressed the cell growth in multiple TNBC cell lines and primary patient TNBC cells., Competing Interests: The authors declare the following competing financial interest(s): J.J. is a cofounder and equity shareholder in Cullgen, Inc. and a consultant for Cullgen, Inc., EpiCypher, Inc., and Accent Therapeutics, Inc. The Jin laboratory received research funds from Celgene Corporation, Levo Therapeutics, Inc., Cullgen, Inc., and Cullinan Oncology, Inc., (© 2022 American Chemical Society.)

Activation and polarization of microglia are involved in neuroinflammation and regulate ischemic stroke-associated brain injury. Protein arginine methyltransferase 8 functions as a regulatory component of hypoxic stress-induced neuroinflammation. The protective effect of protein arginine methyltransferase 8 (PRMT8) against ischemic stroke-associated brain injury through regulation of microglia activation and polarization was investigated. First, PRMT8 was downregulated in middle cerebral artery occlusion (MCAO)-induced mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y. Injection with AAV-PRMT8 reduced infarct volumes in MCAO-induced mice. Moreover, injection with AAV-PRMT8 promoted neuronal survival and ameliorated histopathological changes in the brains of MCAO-induced mice. The neuronal apoptosis and neuroinflammation in MCAO-induced mice were suppressed by AAV-PRMT8 injection. Second, PRMT8 overexpression increased cell viability and suppressed the cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. Third, injection with AAV-PRMT8 reduced almost 50% of CD86 + M1 microglia and enhanced about 20% of CD206 + M2 microglia. Furthermore, PRMT8 overexpression attenuated OGD/R-induced M1 phenotype polarization of BV2. Lastly, PRMT8 upregulated Lin28a and loss of Lin28a attenuated PRMT8 overexpression-induced increase in cell viability and decrease in cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. In conclusion, PRMT8 promoted M2 phenotype polarization of microglia and suppressed neuronal apoptosis to ameliorate cerebral ischemia/reperfusion injury through upregulation of Lin28a.

Objective: To prospectively study the application effect of traditional Chinese medicine (TCM) anticancer decoction with basic chemotherapy and nursing intervention on oral cancer patients after surgery and the effect on tumor markers and immune function., Methods: Eighty-four postoperative oral cancer patients in our hospital from May 2017 to February 2019 were selected and divided into observation group (42 cases) and control group (42 cases). The control group was treated with basic chemotherapy combined with basic nursing care, and the observation group was treated with TCM anticancer decoction and comprehensive nursing intervention on the basis of the control group. The clinical efficacy, the occurrence of adverse reactions, the satisfaction of nursing care, and the two-year cumulative survival rate of the two groups were compared. The immune function, tumor marker level, VAS score, QoR40 score, and survival quality score of the two groups were compared before and after nursing care., Results: The total clinical treatment efficiency of the observation group (88.10%) was significantly higher than that of the control group (69.05%), and the differences between the two groups in oral cleanliness, aspiration frequency, and oral comfort were statistically significant ( P < 0.05). The differences in the occurrence of halitosis, oral fungal infection, leukopenia, gastrointestinal reaction, and fever in the observation group were statistically significant compared with the control group ( P < 0.05). The nursing satisfaction rate in the observation group (95.24%) was significantly higher than that in the control group (78.57%). The two-year cumulative survival rate of the observation group (92.86%) was significantly higher than that of the control group (73.81%). After nursing care, CD4+, CD4+/CD8+, VAS scores, QoR40 scores, and quality of survival scores in both groups all increased, and CD8+, CD56+, CEA level, NSE level, and CA19-9 level all decreased (all P < 0.05)., Conclusion: The clinical efficacy of TCM anticancer decoction with basic chemotherapy and nursing interventions in the treatment of postoperative oral cancer patients was remarkable, which could significantly improve patients' oral cleanliness and comfort, reduce the frequency of sputum aspiration, improve patients' immunity, reduce tumor marker levels, inhibit tumor activity, improve patients' nursing satisfaction, further improve patients' treatment compliance, reduce patients' pain level, improve patients' survival quality, and prolong patients' survival time with high safety. It could be used as a theoretical basis for subsequent clinical research., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Dan Jiang et al.)

Background: Conflicting results have been revealed on the relationship between PSMA uptake values (SUVs) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) and prostate cancer (PCa) aggressiveness. This study is to validate the relationship between SUVs with PCa aggressiveness and its role in evaluation of clinically significant PCa (csPCa) and risk stratification., Methods: We retrospectively enrolled 51 patients who underwent [68Ga]-PSMA PET/CT (PET/CT) before radical prostatectomy (RP). PET/CT results were corrected with whole mount histology. The relationship between SUVs and aggressiveness related indictors including Gleason score, T stage, initial PSA and tumor size were analyzed. The cutoff value for detection of overall PCa, csPCa and intermediate/high-risk PCa were calculated by receiver operating characteristics (ROC) analysis., Results: Both SUVmax and SUVmean positively correlated with Gleason score (SUVmax Spearman r=0.546 P<0.01, SUVmean Spearman r=0.359 P<0.01), PSA level (SUVmax Spearman r=0.568 P<0.01, SUVmean Spearman r=0.529 P<0.01) and tumor volume SUVmax Spearman r=0.635 P<0.01, SUVmean Spearman r=0.590 P<0.01). Tumors with T3 stage had significant higher SUV uptake than T2 (SUVmax 17.49±10.50 vs 9.90±8.7, P<0.01 and SUVmean 17.49±10.50 vs 9.90±8.7, P<0.01). ROC analysis showed cutoff of SUVmax (3.8) and SUVmean (2.8) for overall PCa detection. ROC analysis showed that csPCa and intermediate/high risk PCa had the same cutoff on both SUVmax (8.4) and SUVmean (6.8)., Conclusions: PSMA uptake on PSMA PET/CT positively correlated with Gleason score, T stage, initial PSA and tumor volume. Both SUVmax and SUVmean can be applied as parameters for csPCa detection and risk classification.