Quantitative evaluation of radiation-induced heart disease in patients with lung cancer: a three-dimensional speckle tracking imaging study.

Background: Adverse cardiovascular events due to radiation-induced heart disease (RIHD) have become the leading cause of death in cancer survivors, and early screening for RIHD has become an important clinical issue. Our objective was to determine the utility of three-dimensional speckle tracking echocardiography (3D-STE) for detecting RIHD. Methods: According to inclusion and exclusion criteria, patients with lung cancer who received radiotherapy in our hospital for the first time were recruited as subjects. All subjects underwent the conventional echocardiography and 3D-STE examination at six time points (1 day before radiotherapy, 2.5-3 and 5-6 weeks after beginning radiotherapy, and 3-, 6- and 12-month after ending radiotherapy). Routine electrocardiogram, serum cardiac troponin I (cTnI) and clinical data were detected simultaneously. Results: A total of 105 patients with lung cancer were included in the study. Conventional echocardiography found a small amount of pericardial effusion occurred in 8 subjects at 5-6 weeks after beginning radiotherapy. 3D-STE showed that, compared with before radiotherapy, the absolute values of global longitudinal strain (GLS) and global strain (GS) were significantly decreased at 5-6 weeks after beginning radiotherapy (PGLS<0.001, PGS=0.002), and the absolute values of GLS, global radial strain, global circumferential strain, GS were gradually decreased further at 3-, 6- and 12-month after ending radiotherapy (P<0.001). Electrocardiograph showed that 32 subjects had electrocardiograph abnormalities during radiotherapy and 3 had electrocardiograph abnormalities at 3-month after ending radiotherapy, and most returned to normal within 6 months after ending radiotherapy. Conclusions: Patients with lung cancer undergoing radiation therapy have shown a decrease in the function of the left ventricle of the heart while receiving treatment. Combining the assessment of cTnI with GLS can enhance the early detection of radiation-induced heart damage.

Local Anesthetic Bupivacaine Inhibits Melanoma Proliferation and Metastasis by Targeting PAPSS2.

BACKGROUND: Melanoma is a highly invasive skin cancer with limited treatment strategies. Bupivacaine, a commonly used local anesthetic recognized for its safety, has shown promise in combating tumors. 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) is a key enzyme in the sulfation process and is associated with the development and metastasis of various tumors. This study aimed to explore the mechanism by which bupivacaine inhibits melanoma proliferation and metastasis by targeting PAPSS2. METHODS: The effects of bupivacaine on the proliferation of A375 and A2058 melanoma cells were evaluated using Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) labeling, and clonogenic assays. Cell migration, invasion, and PAPSS2 expression were evaluated using Transwell experiments and Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis. Additionally, an in vivo melanoma tumor model in nude mice was constructed to evaluate the impact of bupivacaine on melanoma growth and metastasis. Immunohistochemistry was used to assess tumor metastasis and PAPSS2 expression levels in the nude mouse model. RESULTS: Experimental results demonstrated that bupivacaine significantly inhibited melanoma proliferation and invasion compared to the control group. Notably, this inhibitory effect was partially reversed by PAPSS2 overexpression. In vivo experiments demonstrated that bupivacaine-treated nude mice exhibited reduced tumor volumes, weights, and fewer lung metastatic foci. Molecular analysis via qRT-PCR and immunohistochemistry analysis further indicated that bupivacaine significantly reduced PAPSS2 in tumor tissues. CONCLUSION: This study confirms that bupivacaine, a local anesthetic, can inhibit melanoma proliferation and metastasis by targeting the PAPSS2 signaling pathway. These findings suggest its potential as an anti-tumor medication and present new treatment strategies for melanoma.

The Early On-treatment Stiffness Decline Attributed to the Improved Hepatic Inflammation in Fibrotic Chronic Hepatitis B.

OBJECTIVES: Hepatic inflammation, the driver of fibrosis progression in liver disease, can impact the accuracy of liver stiffness measurement (LSM). We wondered whether the decline in LSM value during the early antiviral phase was mainly attributed to the control of hepatic inflammation or the regression of fibrosis in patients with fibrotic/cirrhotic chronic hepatitis B (CHB). PATIENTS AND METHODS: The study cohort was composed of 82 patients with CHB who underwent antiviral and antifibrotic therapy at the Fifth Medical Center of PLA General Hospital. All patients had liver biopsies at both baseline and 72 weeks posttherapy. Liver pathology and clinical data, including the LSM value, were collected. RESULTS: After 72 weeks of treatment, both the histologic activity index score and fibrosis score, as well as the LSM value, were significantly decreased (P < 0.001), compared with their baseline values. The pretreatment correlation of LSM value with either histologic activity index score (r = 0.526 vs r = 0.286) or fibrosis score (r = 0.677 vs r = 0.587) was attenuated at 72 weeks. Notably, logistic regression analysis revealed that the improvement in inflammation (odds ratio = 1.018, 95% CI: 1.002-1.031, P = 0.023) but not fibrosis (odds ratio = 0.994, 95% CI: 0.980-1.009, P = 0.414), had an impact on the change in LSM values between baseline and at 72-week treatment. CONCLUSIONS: The findings of this study suggest that in patients with fibrotic CHB receiving antiviral medication, the early phase reduction in LSM value was related to improved hepatic inflammation rather than fibrosis regression.

High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

Binder-Free Three-Dimensional Porous Graphene Cathodes via Self-Assembly for High-Capacity Lithium-Oxygen Batteries.

The porous architectures of oxygen cathodes are highly desired for high-capacity lithium-oxygen batteries (LOBs) to support cathodic catalysts and provide accommodation for discharge products. However, controllable porosity is still a challenge for laminated cathodes with cathode materials and binders, since polymer binders usually shield the active sites of catalysts and block the pores of cathodes. In addition, polymer binders such as poly(vinylidene fluoride) (PVDF) are not stable under the nucleophilic attack of intermediate product superoxide radicals in the oxygen electrochemical environment. The parasitic reactions and blocking effect of binders deteriorate and then quickly shut down the operation of LOBs. Herein, the present work proposes a binder-free three-dimensional (3D) porous graphene (PG) cathode for LOBs, which is prepared by the self-assembly and the chemical reduction of GO with triblock copolymer soft templates (Pluronic F127). The interconnected mesoporous architecture of resultant 3D PG cathodes achieved an ultrahigh capacity of 10,300 mAh g-1 for LOBs. Further, the cathodic catalysts ruthenium (Ru) and manganese dioxide (MnO2) were, respectively, loaded onto the inner surface of PG cathodes to lower the polarization and enhance the cycling performance of LOBs. This work provides an effective way to fabricate free-standing 3D porous oxygen cathodes for high-performance LOBs.

Occurrence and Prioritization of Human Androgen Receptor Disruptors in Sewage Sludges Across China.

The global practice of reusing sewage sludge in agriculture and its landfill disposal reintroduces environmental contaminants, posing risks to human and ecological health. This study screened sewage sludge from 30 Chinese cities for androgen receptor (AR) disruptors, utilizing a disruptor list from the Toxicology in the 21st Century program (Tox21), and identified 25 agonists and 33 antagonists across diverse use categories. Predominantly, natural products 5α-dihydrotestosterone and thymidine emerged as agonists, whereas the industrial intermediate caprolactam was the principal antagonist. In-house bioassays for identified disruptors displayed good alignment with Tox21 potency data, validating employing Tox21 toxicity data for theoretical toxicity estimations. Potency calculations revealed 5α-dihydrotestosterone and two pharmaceuticals (17ß-trenbolone and testosterone isocaproate) as the most potent AR agonists and three dyes (rhodamine 6G, Victoria blue BO, and gentian violet) as antagonists. Theoretical effect contribution evaluations prioritized 5α-dihydrotestosterone and testosterone isocaproate as high-risk AR agonists and caprolactam, rhodamine 6G, and 8-hydroxyquinoline (as a biocide and a preservative) as key antagonists. Notably, 16 agonists and 20 antagonists were newly reported in the sludge, many exhibiting significant detection frequencies, concentrations, and/or toxicities, demanding future scrutiny. Our study presents an efficient strategy for estimating environmental sample toxicity and identifying key toxicants, thereby supporting the development of appropriate sludge management strategies.

Effect-directed analysis of androgenic compounds from sewage sludges in China.

The safety of municipal sewage sludge has raised great concerns because of the accumulation of large-scale endocrine disrupting chemicals in the sludge during wastewater treatment. The presence of contaminants in sludge can cause secondary pollution owing to inappropriate disposal mechanisms, posing potential risks to the environment and human health. Effect-directed analysis (EDA), involving an androgen receptor (AR) reporter gene bioassay, fractionation, and suspect and nontarget chemical analysis, were applied to identify causal AR agonists in sludge; 20 of the 30 sludge extracts exhibited significant androgenic activity. Among these, the extracts from Yinchuan, Kunming, and Shijiazhuang, which held the most polluted AR agonistic activities were prepared for extensive EDA, with the dihydrotestosterone (DHT)-equivalency of 2.5 - 4.5 ng DHT/g of sludge. Seven androgens, namely boldione, androstenedione, testosterone, megestrol, progesterone, and testosterone isocaproate, were identified in these strongest sludges together, along with testosterone cypionate, first reported in sludge media. These identified androgens together accounted for 55 %, 87 %, and 52 % of the effects on the sludge from Yinchuan, Shijiazhuang, and Kunming, respectively. This study elucidates the causative androgenic compounds in sewage sludge and provides a valuable reference for monitoring and managing androgens in wastewater treatment.

Engineered extracellular vesicles for delivering functional Cas9/gRNA to eliminate hepatitis B virus cccDNA and integration.

The persistence of HBV covalently closed circular DNA (cccDNA) and HBV integration into the host genome in infected hepatocytes pose significant challenges to the cure of chronic HBV infection. Although CRISPR/Cas9-mediated genome editing shows promise for targeted clearance of viral genomes, a safe and efficient delivery method is currently lacking. Here, we developed a novel approach by combining light-induced heterodimerization and protein acylation to enhance the loading efficiency of Cas9 protein into extracellular vesicles (EVs). Moreover, vesicular stomatitis virus-glycoprotein (VSV-G) was incorporated onto the EVs membrane, significantly facilitating the endosomal escape of Cas9 protein and increasing its gene editing activity in recipient cells. Our results demonstrated that engineered EVs containing Cas9/gRNA and VSV-G can effectively reduce viral antigens and cccDNA levels in the HBV-replicating and infected cell models. Notably, we also confirmed the antiviral activity and high safety of the engineered EVs in the HBV-replicating mouse model generated by hydrodynamic injection and the HBV transgenic mouse model. In conclusion, engineered EVs could successfully mediate functional CRISPR/Cas9 delivery both in vitro and in vivo, leading to the clearance of episomal cccDNA and integrated viral DNA fragments, and providing a novel therapeutic approach for curing chronic HBV infection.

Identification and Coexposure of Neonicotinoid Insecticides and Their Transformation Products in Retail Cowpea (Vigna unguiculata).

There is growing evidence that the transformation products of emerging contaminants in foodstuffs may pose a health risk to humans. However, the exact identities, levels, and estimated dietary intake (EDI) of neonicotinoid transformation products in crops remain poorly understood. We established an extended suspect screening strategy to investigate neonicotinoid insecticides and their transformation products in retail cowpea from 11 cities in Hainan Province, China. Forty-nine transformation products were identified in retail cowpea, of which 22-36 were found in 98.6% of the samples. Notably, 31 new transformation products were derived from new processes or a combination of different transformation processes. The mean concentrations of neonicotinoids and nine of the transformation products (with authentic standards) were in the ranges of 0.0824-5.34 and 0.0636-1.50 ng/g, respectively. The cumulative EDIs of the quantified transformation products were lower than those of parent neonicotinoids with the exception of clothianidin desmethyl, which had a ratio of 1157%. However, the coexistence of the other 40 transformation products (without authentic standards) in cowpea suggested that the exposure risk from all of the transformation products might be higher. This study demonstrated that pesticide transformation products should be considered in food chain risk assessments and included in future regulatory management.

Sirtuin4 alleviates severe acute pancreatitis by regulating HIF-1α/HO-1 mediated ferroptosis.

Acute pancreatitis (AP) is a common emergency of the digestive system and serious cases can develop into severe acute pancreatitis (SAP), which ortality rates up to 30%. Sirtuin4 (SIRT4) is a member of the sirtuin family, and plays a key role in inflammation and oxidative stress. However, the potential role of SIRT4 in SAP has yet to be elucidated. In the present study, we found that the expression level of SIRT4 in human AP was downregulated by screening a public database, suggesting that SIRT4 may play a role in AP. Subsequently, we used L-arginine (L-Arg) to induce SAP in SIRT4 knockout (SIRT4_KO) and SIRT4 overexpression (AAV_SIRT4) mice. The results showed that the pancreatic tissue injury and related lung and kidney injury were serious in SIRT4_KO mice after SAP induction, but were significantly reduced in AAV_SIRT4 mice. More importantly, we found that the levels of antioxidant factors GSH and SOD were decreased in SIRT4_KO mice, and the production of oxidative products and lipid peroxidation markers was increased, suggesting that SIRT4 was involved in inflammation and oxidative stress during SAP. Further studies showed that the absence or overexpression of SIRT4 affected the expression level of Hypoxia-inducible factor-1α (HIF-1α) after SAP induction, and regulated the expression of ferroptosis related proteins by mediating HIF-1α/HO-1 pathway. Collectively, our study revealed that SIRT4 plays a protective role in SAP by regulating the HIF-1α/HO-1 pathway to inhibit ferroptosis.

Cloning of the wheat leaf rust resistance gene Lr47 introgressed from Aegilops speltoides.

Leaf rust, caused by Puccinia triticina Eriksson (Pt), is one of the most severe foliar diseases of wheat. Breeding for leaf rust resistance is a practical and sustainable method to control this devastating disease. Here, we report the identification of Lr47, a broadly effective leaf rust resistance gene introgressed into wheat from Aegilops speltoides. Lr47 encodes a coiled-coil nucleotide-binding leucine-rich repeat protein that is both necessary and sufficient to confer Pt resistance, as demonstrated by loss-of-function mutations and transgenic complementation. Lr47 introgression lines with no or reduced linkage drag are generated using the Pairing homoeologous1 mutation, and a diagnostic molecular marker for Lr47 is developed. The coiled-coil domain of the Lr47 protein is unable to induce cell death, nor does it have self-protein interaction. The cloning of Lr47 expands the number of leaf rust resistance genes that can be incorporated into multigene transgenic cassettes to control this devastating disease.

Corrigendum: Machine learning prediction model for post- hepatectomy liver failure in hepatocellular carcinoma: a multicenter study.

[This corrects the article DOI: 10.3389/fonc.2022.986867.].

Microbiota of long-term indwelling hemodialysis catheters during renal transplantation perioperative period: a cross-sectional metagenomic microbial community analysis.

Background: Catheter-related infection (CRI) is a major complication in patients undergoing hemodialysis. The lack of high-throughput research on catheter-related microbiota makes it difficult to predict the occurrence of CRI. Thus, this study aimed to delineate the microbial structure and diversity landscape of hemodialysis catheter tips among patients during the perioperative period of kidney transplantation (KTx) and provide insights into predicting the occurrence of CRI.Methods: Forty patients at the Department of Transplantation undergoing hemodialysis catheter removal were prospectively included. Samples, including catheter tip, catheter outlet skin swab, catheter blood, peripheral blood, oropharynx swab, and midstream urine, from the separate pre- and post-KTx groups were collected and analyzed using metagenomic next-generation sequencing (mNGS). All the catheter tips and blood samples were cultured conventionally.Results: The positive detection rates for bacteria using mNGS and traditional culture were 97.09% (200/206) and 2.65% (3/113), respectively. Low antibiotic-sensitivity biofilms with colonized bacteria were detected at the catheter tip. In asymptomatic patients, no statistically significant difference was observed in the catheter tip microbial composition and diversity between the pre- and post-KTx group. The catheter tip microbial composition and diversity were associated with fasting blood glucose levels. Microorganisms at the catheter tip most likely originated from catheter outlet skin and peripheral blood.Conclusions: The long-term colonization microbiota at the catheter tip is in a relatively stable state and is not readily influenced by KTx. It does not act as the source of infection in all CRIs, but could reflect hematogenous infection to some extent.

Assessment of the relationships between invasive endocervical adenocarcinoma and human papillomavirus infection and distribution characteristics in China: According to the new WHO classification criteria in 2020.

OBJECTIVE: To assess the association between endocervical adenocarcinoma (ECA) and HPV (Human papillomavirus) infection, as well as the characteristics of ECA distribution in China. METHODS: A total of 756 specimens were collected from seven geographic regions across China. All cases were histologically categorized according to the 2020 WHO classification of female genital tract cancers, and 496 cases were included. We performed the SPF10-DEIA-LiPA25 assay on all specimens' whole tissue sections using PCR (WTS-PCR) to detect HPV DNA and 141 WTS-PCR HPV-positive specimens were selected for the laser capture microdissection (LCM). RESULTS: Four predominant prevalent histological categories of ECA in China were usual type (51.8%, 257), invasive stratified mucin-producing carcinoma (iSMILE) (11.5%, 57), mucinous NOS (not otherwise specid) (10.3%, 51), and gastric type (7.9%, 39). HPV positivity was 91.4% (235/257), 100.0% (57/57), and 90.2% (46/51) in usual type, iSMILE, and mucinous NOS by WTS-PCR detection, respectively (P < 0.001). LCM-PCR results showed a decreasing trend in HPV DNA positivity, and 21 (95.5%) patients with HPV-I were negative for HPV-DNA in glandular epithelial tissue. The most prevalent HPV genotypes in ECA were HPV16 (47.5%), 18 (40.8%), and 52 (6.5%). The average age of patients with HPVA was 44.9 years, while that of patients with HPV-I was 49.1 years, HPVA is more prevalent in younger females in China (P < 0.001). CONCLUSIONS: In China, the predominant prevalent histological category of ECA is the usual type of adenocarcinoma, followed by iSMILE. Additionally, patients with HPVA tended to be younger than those with HPV-I.

Practical application guide for the discovery of novel PFAS in environmental samples using high resolution mass spectrometry.

BACKGROUND: The intersection of the topics of high-resolution mass spectrometry (HRMS) and per- and polyfluoroalkyl substances (PFAS) bring together two disparate and complex subjects. Recently non-targeted analysis (NTA) for the discovery of novel PFAS in environmental and biological media has been shown to be valuable in multiple applications. Classical targeted analysis for PFAS using LC-MS/MS, though growing in compound coverage, is still unable to inform a holistic understanding of the PFAS burden in most samples. NTA fills at least a portion of this data gap. OBJECTIVES: Entrance into the study of novel PFAS discovery requires identification techniques such as HRMS (e.g., QTOF and Orbitrap) instrumentation. This requires practical knowledge of best approaches depending on the purpose of the analyses. The utility of HRMS applications for PFAS discovery is unquestioned and will likely play a significant role in many future environmental and human exposure studies. METHODS/RESULTS: PFAS have some characteristics that make them standout from most other chemicals present in samples. Through a series of tell-tale PFAS characteristics (e.g., characteristic mass defect range, homologous series and characteristic fragmentation patterns), and case studies different approaches and remaining challenges are demonstrated. IMPACT STATEMENT: The identification of novel PFAS via non-targeted analysis using high resolution mass spectrometry is an important and difficult endeavor. This synopsis document will hopefully make current and future efforts on this topic easier to perform for novice and experienced alike. The typical time devoted to NTA PFAS investigations (weeks to months or more) may benefit from these practical steps employed.

Dynamic viral integration patterns actively participate in the progression of BK polyomavirus-associated diseases after renal transplantation.

The classical lytic infection theory along with large T antigen-mediated oncogenesis cannot explain the BK polyomavirus (BKPyV)-associated tumor secondary to BKPyV-associated nephropathy (BKVAN), viremia/DNAemia, and viruria after renal transplantation. This study performed virome capture sequencing and pathological examination on regularly collected urine sediment and peripheral blood samples, and BKVAN and tumor biopsy tissues of 20 patients with BKPyV-associated diseases of different stages. In the early noncancerous stages, well-amplified integration sites were visualized by in situ polymerase chain reaction, simultaneously with BKPyV inclusion bodies and capsid protein expression. The integration intensity, the proportion of microhomology-mediated end-joining integration, and host PARP-1 and POLQ gene expression levels increased with disease progression. Furthermore, multiomics analysis was performed on BKPyV-associated urothelial carcinoma tissues, identifying tandem-like structures of BKPyV integration using long-read genome sequencing. The carcinogenicity of BKPyV integration was proven to disturb host gene expression and increase viral oncoprotein expression. Fallible DNA double-strand break repair pathways were significantly activated in the parenchyma of BKPyV-associated tumors. Olaparib showed an antitumor activity dose-response effect in the tumor organoids without BRCA1/2 genes mutation. In conclusion, the dynamic viral integration patterns actively participate in the progression of BKPyV-associated diseases and thus could be a potential target for disease monitoring and intervention.

Renaissance of elemental phosphorus materials: properties, synthesis, and applications in sustainable energy and environment.

The polymorphism of phosphorus-based materials has garnered much research interest, and the variable chemical bonding structures give rise to a variety of micro and nanostructures. Among the different types of materials containing phosphorus, elemental phosphorus materials (EPMs) constitute the foundation for the synthesis of related compounds. EPMs are experiencing a renaissance in the post-graphene era, thanks to recent advancements in the scaling-down of black phosphorus, amorphous red phosphorus, violet phosphorus, and fibrous phosphorus and consequently, diverse classes of low-dimensional sheets, ribbons, and dots of EPMs with intriguing properties have been produced. The nanostructured EPMs featuring tunable bandgaps, moderate carrier mobility, and excellent optical absorption have shown great potential in energy conversion, energy storage, and environmental remediation. It is thus important to have a good understanding of the differences and interrelationships among diverse EPMs, their intrinsic physical and chemical properties, the synthesis of specific structures, and the selection of suitable nanostructures of EPMs for particular applications. In this comprehensive review, we aim to provide an in-depth analysis and discussion of the fundamental physicochemical properties, synthesis, and applications of EPMs in the areas of energy conversion, energy storage, and environmental remediation. Our evaluations are based on recent literature on well-established phosphorus allotropes and theoretical predictions of new EPMs. The objective of this review is to enhance our comprehension of the characteristics of EPMs, keep abreast of recent advances, and provide guidance for future research of EPMs in the fields of chemistry and materials science.