Epigenetic targeting of PGBD5-dependent DNA damage in SMARCB1-deficient sarcomas.

Despite the potential of targeted epigenetic therapies, most cancers do not respond to current epigenetic drugs. The Polycomb repressive complex EZH2 inhibitor tazemetostat was recently approved for the treatment of SMARCB1 -deficient epithelioid sarcomas, based on the functional antagonism between PRC2 and loss of SMARCB1. Through the analysis of tazemetostat-treated patient tumors, we recently defined key principles of their response and resistance to EZH2 epigenetic therapy. Here, using transcriptomic inference from SMARCB1 -deficient tumor cells, we nominate the DNA damage repair kinase ATR as a target for rational combination EZH2 epigenetic therapy. We show that EZH2 inhibition promotes DNA damage in epithelioid and rhabdoid tumor cells, at least in part via its induction of the transposase-derived PGBD5. We leverage this collateral synthetic lethal dependency to target PGBD5-dependent DNA damage by inhibition of ATR but not CHK1 using elimusertib. Consequently, combined EZH2 and ATR inhibition improves therapeutic responses in diverse patient-derived epithelioid and rhabdoid tumors in vivo . This advances a combination epigenetic therapy based on EZH2-PGBD5 synthetic lethal dependency suitable for immediate translation to clinical trials for patients.

Significant influence of urban human activities and marine input on rainwater chemistry in a coastal large city, China.

The coastal urban region is generally considered an atmospheric receptor for terrestrial and marine input materials, and rainfall chemistry can trace the wet scavenging process of these materials. Fast urbanization in China's east coastal areas has greatly altered the rainwater chemistry. However, the chemical variations, determinants, and sources of rainfall are unclear. Therefore, the typical coastal city of Fuzhou was selected for 1-year rainwater sampling and inorganic ions were detected to explore above problems. The findings depicted that rainwater ions in Fuzhou were slightly different from those in other coastal cities. Although NO3-, SO42-, Ca2+ and NH4+ dominated the rainwater ions, the marine input Cl- (22 %) and Na+ (11 %) also contributed a considerable percentage to the rainwater ions. Large differences in ion concentrations (2∼28 times) were found in monthly scale due to the rainfall amount. Both natural and anthropogenic determinants influenced the rainwater ions in coastal cities, such as SO2 emission, air SO2 and PM10 content on rainwater SO42-, NO3-, and Ca2+, and soot & dust emission on rainwater SO42-, NO3-, indicating the vital contribution of human activities. Stoichiometry and positive matrix factorization-based sources identification indicated that atmospheric dust/particles were the primary contributor of Ca2+ (83.3 %) and F- (83.7 %), and considerable contributor of SO42- (39.5 %), NO3- (38.3 %) and K+ (41.5 %). Anthropogenic origins, such as urban waste volatilization and fuel combustion emission, contributed 95 % of NH4+, 54.5 % of NO3- and 41.9 % of SO42-, and the traffic sources contribution was relatively higher than fixed emission sources. The marine input represented the vital source of Cl- (77.7 %), Na+ (84.9 %), and Mg2+ (55.3 %). This work highlights the significant influence of urban human activities and marine input on rainwater chemicals and provides new insight into the material cycle between the atmosphere and earth-surface in coastal city.

Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches.

A special microenvironment called the "pre-metastatic niche" is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches by secreting pro-metastatic factors, the underlying molecular mechanisms are still poorly understood. Here, we show that the injection of primary tumor-secreted pro-metastatic factors from B16F10 melanoma or 4T1 breast cancer cells into healthy mice can induce the destruction of the vascular endothelial glycocalyx, which is a polysaccharide coating on the vascular endothelial lumen that normally inhibits tumor cell passage into and out of the circulation. However, when human umbilical vein endothelial cultures were treated in vitro with these secreted pro-metastatic factors, no significant destruction of the glycocalyx was observed, implying that this destruction requires a complex in vivo microenvironment. The tissue section analysis revealed that secreted pro-metastatic factors could clearly upregulate macrophage-related molecules such as CD11b and tumor necrosis factor-α (TNF-α) in the heart, liver, spleen, lung, and kidney, which is associated with the upregulation and activation of heparanase. In addition, macrophage depletion significantly attenuated the degradation of the vascular endothelial glycocalyx induced by secreted pro-metastatic factors. This indicates that the secreted pro-metastatic factors that destroy the vascular endothelial glycocalyx rely primarily on macrophages. Our findings suggest that the formation of pre-metastatic niches involves degradation of the vascular endothelial glycocalyx, which may hence be a useful target for developing therapies to inhibit cancer metastasis.

Organic-Inorganic Hybrid Materials: Tailoring Carbon Dioxide-Based Polycarbonate with POSS-SH Crosslinking.

A novel functional polycarbonate (PAGC), characterized by the presence of double bonds within its side chain, was successfully synthesized through a ternary copolymerization of propylene oxide (PO), allyl glycidyl ether (AGE), and carbon dioxide (CO2). Polyhedral oligomeric silsesquioxanes octamercaptopropyl (POSS-SH) was employed as a crosslinking agent, contributing to the formation of organic-inorganic hybrid materials. This incorporation was facilitated through thiol-ene click reactions, enabling effective interactions between the POSS molecules and the double bonds in the side chains of the polycarbonate. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) confirmed a homogeneous distribution of silicon (Si) and sulfur (S) in the polycarbonate matrix. The thiol-ene click reaction between POSS-SH and the polycarbonate led to a micro-crosslinked structure. This enhancement significantly increased the tensile strength of the polycarbonate to 42 MPa, a notable improvement over traditional poly (propylene carbonate) (PPC). Moreover, the cross-linked structure exhibited enhanced solvent resistance, expanding the potential applications of these polycarbonates in various plastic materials.

Association between air pollution and male sexual function: A nationwide observational study in China.

This study aimed to explore the associations between air pollution and male sexual function. A total of 5047 male subjects in China were included in this study. The average air pollution exposure (PM2.5, PM10, SO2, CO, NO2, and O3) for the preceding 1, 3, 6, and 12 months before the participants' response was assessed. Male sexual function was evaluated using the International Index of Erectile Function-5 (IIEF-5) and the Premature Ejaculation Diagnostic Tool (PEDT). Generalized linear models were utilized to explore the associations between air pollution and male sexual function. K-prototype algorithm was conducted to identify the association among specific populations. Significant adverse effects on the IIEF-5 score were observed with NO2 exposure during the preceding 1, 3, and 6 months (1 m: ß = -5.26E-05; 3 m: ß = -4.83E-05; 6 m: ß = -4.23E-05, P < 0.05). PM2.5 exposure during the preceding 12 months was found to significantly negatively affect the PEDT after adjusting for confounding variables. Our research indicated negative correlations between air pollutant exposures and male sexual function for the first time. Furthermore, these associations were more pronounced among specific participants who maintain a normal BMI, exhibit extroverted traits, and currently engage in smoking and alcohol consumption.

In vitro and in vivo study of antibacterial and anti-encrustation coating on ureteric stents.

OBJECTIVES: To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. MATERIALS AND METHODS: Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. RESULTS: The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. CONCLUSIONS: Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.

Case report: remedial microdissection testicular sperm extraction after onco-microdissection testicular sperm extraction failure.

BACKGROUND: Testicular cancer (TC) mostly occurs in men aged 14 to 44. Studies have shown that TC seriously damages male fertility, and 6% to 24% of patients with TC were even found to suffer from azoospermia when they are diagnosed. At present, some studies have pointed out that onco-microdissection testicular sperm extraction (mTESE) can extract sperm from tumor testicles. However, there are almost no reports on remedial measures after onco-mTESE failure. Given the valuable opportunity for fertility preservation in patients with TC and azoospermia, it is necessary to provide effective remedial methods for patients with failed onco-mTESE. METHODS: Two young men, who were diagnosed with TC and also found to have azoospermia, tried onco-mTESE while undergoing radical orchiectomy for fertility preservation. However, sperm extraction failed in both patients. Subsequently, the isolated testicular tissue of the patient in case 1 suffered from TC again, and the patient in case 2 was scheduled to receive multiple cycles of gonadotoxic chemotherapy. Because both had a plan to have a birth in the future, we performed remedial mTESE. RESULTS: Sperm was successfully extracted from both patients. The patient recovered well, without complications. The patient couple in case 1 underwent 1 intracytoplasmic sperm injection (ICSI) cycle but did not achieve clinical pregnancy. CONCLUSIONS: There is still an opportunity to extract sperm successfully using onco-mTESE, despite the difficulty of fertility preservation in TC patients with azoospermia. If sperm extraction from the tumor testis fails, implementing remedial mTESE as early as possible would likely preserve the last chance of fertility for these patients.

Overcoming clinical resistance to EZH2 inhibition using rational epigenetic combination therapy.

Epigenetic dependencies have become evident in many cancers. Based on antagonism between BAF/SWI/SNF and PRC2 in SMARCB1-deficient sarcomas, we recently completed the clinical trial of the EZH2 inhibitor tazemetostat. However, the principles of tumor response to epigenetic therapy in general, and tazemetostat in particular, remain unknown. Using functional genomics and diverse experimental models, we define molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors. We found distinct acquired mutations that converge on the RB1/E2F axis and decouple EZH2-dependent differentiation and cell cycle control. This allows tumor cells to escape tazemetostat-induced G1 arrest, suggests a general mechanism for effective therapy, and provides prospective biomarkers for therapy stratification, including PRICKLE1. Based on this, we develop a combination strategy to circumvent tazemetostat resistance using bypass targeting of AURKB. This offers a paradigm for rational epigenetic combination therapy suitable for translation to clinical trials for epithelioid sarcomas, rhabdoid tumors, and other epigenetically dysregulated cancers.

Exploration of natural processes and anthropogenic inputs by Zn isotopes in suspended particulate matter: A case study from the Lancang River in Southwest China.

River is an important pathway for the biogeochemical cycle of Zn. This study reports Zn concentration and δ66Zn composition for suspended particulate matter (SPM) from Lancang River basin in Southwest China, and explore the impact of natural processes and human activities on Zn cycle. The SPM samples have a much higher average Zn content (162 mg kg-1) than that of the upper crust (67.0 mg kg-1), but it is close to the value of the Pearl River (187 mg kg-1). The enrichment factor (EF) values of Zn in SPM range from 1.08 to 6.88, with an average of 2.15, which does not show significant pollution characteristics. The δ66Zn values in SPM range from -0.67‰ to +0.63‰, with an average of +0.13‰. The δ66Zn values showed positive correlation with Ca/Mg ratios while showed little correlation with Zn contents in SPM. It indicated that anthropogenic sources have limited influence on SPM, and the Zn isotope composition in SPM is more likely to be inherited from the weathered rocks materials and influenced by natural fractionation processes in river water. This result contributes to understanding of the geochemical cycling process of Zn and its environmental effects in water.

MicroRNA-483-3p Inhibitor Ameliorates Sepsis-Induced Intestinal Injury by Attenuating Cell Apoptosis and Cytotoxicity Via Regulating HIPK2.

Sepsis is a life-threatening syndrome that can result in multi-organ dysfunction. MicroRNA (miR)-483-3p was previously demonstrated to be upregulated in sepsis patients; however, its specific functions in sepsis-triggered intestinal injury remain unclarified. Human intestinal epithelial NCM460 cell line was stimulated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury in vitro. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was utilized for examining cell apoptosis. Western blotting and real time quantitative polymerase chain reaction (RT-qPCR) were used for detecting molecular protein and RNA levels. LPS-induced cytotoxicity was determined by measuring concentrations of lactate dehydrogenase (LDH), diamine oxidase (DAO) and fatty acid binding protein 2 (FABP2). Luciferase reporter assay was utilized for verifying the interaction between miR-483-3p and homeodomain interacting protein kinase 2 (HIPK2). Inhibiting miR-483-3p alleviates LPS-triggered NCM460 cell apoptosis and cytotoxicity. miR-483-3p targeted HIPK2 in LPS-stimulated NCM460 cells. Knockdown of HIPK2 reversed the above effects mediated by miR-483-3p inhibitor. Inhibiting miR-483-3p ameliorates LPS-triggered apoptosis and cytotoxicity by targeting HIPK2.

Genetic mechanisms of fertilization failure and early embryonic arrest: a comprehensive review.

BACKGROUND: Infertility and pregnancy loss are longstanding problems. Successful fertilization and high-quality embryos are prerequisites for an ongoing pregnancy. Studies have proven that every stage in the human reproductive process is regulated by multiple genes and any problem, at any step, may lead to fertilization failure (FF) or early embryonic arrest (EEA). Doctors can diagnose the pathogenic factors involved in FF and EEA by using genetic methods. With the progress in the development of new genetic technologies, such as single-cell RNA analysis and whole-exome sequencing, a new approach has opened up for us to directly study human germ cells and reproductive development. These findings will help us to identify the unique mechanism(s) that leads to FF and EEA in order to find potential treatments. OBJECTIVE AND RATIONALE: The goal of this review is to compile current genetic knowledge related to FF and EEA, clarifying the mechanisms involved and providing clues for clinical diagnosis and treatment. SEARCH METHODS: PubMed was used to search for relevant research articles and reviews, primarily focusing on English-language publications from January 1978 to June 2023. The search terms included fertilization failure, early embryonic arrest, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, non-coding RNA, and other related keywords. Additional studies were identified by searching reference lists. This review primarily focuses on research conducted in humans. However, it also incorporates relevant data from animal models when applicable. The results were presented descriptively, and individual study quality was not assessed. OUTCOMES: A total of 233 relevant articles were included in the final review, from 3925 records identified initially. The review provides an overview of genetic factors and mechanisms involved in the human reproductive process. The genetic mutations and other genetic mechanisms of FF and EEA were systematically reviewed, for example, globozoospermia, oocyte activation failure, maternal effect gene mutations, zygotic genome activation abnormalities, chromosome abnormalities, and epigenetic abnormalities. Additionally, the review summarizes progress in treatments for different gene defects, offering new insights for clinical diagnosis and treatment. WIDER IMPLICATIONS: The information provided in this review will facilitate the development of more accurate molecular screening tools for diagnosing infertility using genetic markers and networks in human reproductive development. The findings will also help guide clinical practice by identifying appropriate interventions based on specific gene mutations. For example, when an individual has obvious gene mutations related to FF, ICSI is recommended instead of IVF. However, in the case of genetic defects such as phospholipase C zeta1 (PLCZ1), actin-like7A (ACTL7A), actin-like 9 (ACTL9), and IQ motif-containing N (IQCN), ICSI may also fail to fertilize. We can consider artificial oocyte activation technology with ICSI to improve fertilization rate and reduce monetary and time costs. In the future, fertility is expected to be improved or restored by interfering with or supplementing the relevant genes.

Engineering A Boron-Rich Interphase with Nonflammable Electrolyte toward Stable Li||NCM811 Cells Under Elevated Temperature.

Despite the high energy of LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) cathode, it still suffers serious decay due to the continuous solvents decomposition and unstable cathode electrolyte interphase (CEI) layers, especially under high temperatures. The intense exothermic reaction between delithiated NCM811 and flammable electrolyte, on the other hand, pushes the batteries to their safety limit. Herein, these two issues are tackled via engineering the electrolytes, that is, utilizing salts with higher HOMO levels and nonflammable solvents with lower HOMO levels, to reduce the massive decomposition of solvents and improve battery safety under elevated temperatures. Consequently, a thin and boron-rich CEI is generated, which effectively inhibited the side reactions, thus improving the cycling stability and safety. Deviated from the highly concentrated electrolytes which heavily relies on the usage of massive salts, the electrolyte recipe can introduce a robust inorganic-rich CEI but use much less salt (i.e., dilute electrolyte), and thus, offer an encouraging alternative toward practical applications. As such, the NCM811 cathode exhibits a high-capacity retention of 81.2% after 950 cycles at 25 °C and 75% after 300 cycles at 55 °C. This work provides a universal electrolyte design strategy for designing stable and safe high-temperature electrolytes for the NCM811 cathode.

Whole-Exome Sequencing Analysis of Idiopathic Hypogonadotropic Hypogonadism: Comparison of Varicocele and Nonobstructive Azoospermia.

As a rare disease leading to male infertility, idiopathic hypogonadotropic hypogonadism (IHH) has strong heterogeneity of clinical phenotype and gene mutation. At present, there is no effective diagnosis and treatment method for this disease. This study is to explore the possible new pathogenic gene of idiopathic hypogonadotrophic hypogonadism and the pathological mechanism affecting its occurrence. We performed a whole-exome sequencing on 9 patients with normosmic idiopathic hypogonadotropic hypogonadism (nIHH), 19 varicocele patients with asthenospermia, oligospermia, or azoospermia, 5 patients with simple nonobstructive azoospermia, and 13 normal healthy adult males and carried out comparative analysis, channel analysis, etc. After preliminary sequencing screening, 309-431 genes harbouring variants, including SNPs and indels, were predicted to be harmful per single patient in each group. In genetic variations of nIHH patients' analysis, variants were detected in 10 loci and nine genes in nine patients. And in co-analysis of the three patient groups, nine nIHH patients, 19 VC patients, and five SN patients shared 116 variants, with 28 variant-harbouring genes detected in five or more patients. We found that the NEFH, CCDC177, and PCLO genes and the Gene Ontology pathways GO:0051301: cell division and GO:0090066: regulation of anatomical structure size may be key factors in the pathogenic mechanism of IHH. Our results suggest that the pathogenic mechanism of IHH is not limited to the central nervous system effects of GnRH but may involve other heterogeneous pathogenic genetic variants that affect peripheral organs.

Endoscopic thyroidectomy via areola approach for stage T1 papillary thyroid carcinoma: feasibility, safety, and oncologic outcomes.

Purpose: To evaluate the feasibility, safety, and oncologic outcomes associated with endoscopic thyroidectomy via the areolar approach (ETAA), compared with conventional open thyroidectomy (COT) for the treatment of stage T1 papillary thyroid carcinoma (PTC). Methods: Between January 2021 and June 2022, a total of 1204 patients diagnosed with PTC underwent screening, out of which 138 patients were selected for inclusion in the study population after propensity score matching (92 patients in the ETAA group and 46 patients in the COT group). The study included the collection and analysis of clinicopathologic characteristics, intraoperative outcomes, postoperative outcomes, complications, and follow-up data using R software. Results: The operative time for the ETAA group was longer than that for the COT group (160.42 ± 32.21 min vs. 121.93 ± 29.78 min, p < 0.0001). However, there were no significant differences between the two groups in terms of intraoperative blood loss, the extent of surgical resection, the number of dissected lymph nodes, the number of metastatic lymph nodes, and the rate of parathyroid autotransplantation. Postoperative drainage and C-reactive protein levels were higher in the ETAA group than in the COT group, but there were no significant differences in 24-hour visual analogue scale scores, white blood cell counts, drainage duration, or postoperative hospital stay. Complication rates were similar between the two groups, and no permanent recurrent laryngeal nerve palsy or hypoparathyroidism was observed. Patients who underwent ETAA reported greater cosmetic satisfaction and quality of life than those who underwent COT. During the follow-up phase, only one patient in the COT group developed lateral cervical lymph node involvement requiring reoperation. Conclusion: ETAA is a safe and feasible surgical method for patients with stage T1 PTC, providing results similar to COT in terms of oncologic completeness, while avoiding neck scars, with excellent cosmetic effects. Clinical trial registration: Chinese Clinical Trial Registry center, identifier ChiCTR2300077109.

The overexpression of SlBRI1 driven by Atrd29A promoter-transgenic plants improves the chilling stress tolerance of tomato.

MAIN CONCLUSION: Overexpression of SlBRI1 driven by the Atrd29A promoter could increase the cold resistance of tomato plants during chilling stress but did not improve the expression of SlBRI1 and plant growth under normal conditions. Low temperature is the main limiting factor severely affecting tomato plant development, growth, and fruit quality in winter and spring. Brassinosteroids (BRs) and key BR signaling genes positively regulate tomato plant development and response to chilling stress. Brassinosteroid-insensitive 1 (BRI1) is a major BR receptor that initiates BR signaling. Our results showed that overexpression of SlBRI1 driven by the Atrd29A promoter in transgenic plants did not increase the expression of SlBRI1 under normal conditions but rapidly induced the expression of SlBRI1 during chilling stress. The degree of wilting was lower in Atrd29A promoter-transgenic plants than in wild-type (WT) plants after chilling stress. Atrd29A promoter-transgenic plants exhibited low relative electrolyte leakage and reactive oxygen species (ROS) accumulation under chilling stress. Transgenic plants showed higher photosynthetic ability and antioxidant enzyme activity than WT plants under chilling stress. The BR content and expression levels of key genes involved in BR biosynthesis in Atrd29A-promoter transgenic plants were significantly lower than those in WT plants during chilling stress. The abscisic acid (ABA) content and expression levels of key ABA biosynthesis genes in the Atrd29A promoter-transgenic plants were significantly higher than those in the WT plants during chilling stress. In addition, Atrd29A promoter-transgenic plants positively enhanced the expression levels of ICE-CBF-COR cold-responsive pathway genes. Therefore, the overexpression of SlBRI1 driven by the Atrd29A promoter in transgenic plants can be a valuable tool for reducing chilling stress.

Causal association between body mass index and autoimmune thyroiditis: evidence from Mendelian randomization.

BACKGROUND: Recent studies have reported associations between body mass index (BMI) and various autoimmune disorders. However, it is still uncertain whether there exists a direct cause-and-effect relationship between BMI and autoimmune thyroiditis (AIT). The aim of our study is to investigate the causal association between BMI and AIT. METHODS: We conducted a two-sample summary data Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary statistics data related to BMI as exposure, and GWAS summary statistic data sets for AIT as the outcome. Robustly associated single-nucleotide polymorphisms (SNPs) for BMI were selected as instrumental variables (IVs). We used the inverse variance weighted (IVW) method as the primary method and performed other MR methods such as MR-Egger regression, weighted median, simple mode, and weighted mode analyses for further validation. The slope of MR-Egger regression was used to correct for pleiotropy and provide estimates of causality. The p-value for the intercept in MR-Egger was utilized to detect any directional pleiotropic effects. Heterogeneity and sensitivity analyses were performed to assess the robustness of our findings. RESULTS: Seventy-eight SNPs were selected from GWAS on BMI as the IVs. Our MR analysis using the IVW method showed a potential causal association between BMI and AIT (OR = 3.071, 95% CI 1.324-7.118). Findings from other MR methods are non-significant, although the direction of effect is consistent. There was no evidence that the result was affected by genetic pleiotropy (MR-Egger regression intercept = 0.01, SE = 0.00025, p = 0.719). Heterogeneity and sensitivity analyses revealed no significant heterogeneity among SNPs, and no single SNP drove the observed associations. CONCLUSION: Our findings suggest a potential causal association between BMI and AIT, which may provide a basis for further investigation into the relationship between BMI and AIT. Further studies are required as only the IVW method shows significant results, and the case sample size is small.

Heterogeneous slab thermal dehydration driving warm subduction zone earthquakes.

Changing thermal regime is one of the key mechanisms driving seismogenic behaviors at cold megathrusts, but it is difficult to interpret warm subduction zones such as Vanuatu for the temperatures are higher than that accommodates shallow brittle failures. We construct a 3-D thermomechanical model to clarify the thermal structure that controls tectonic seismicity in Vanuatu and predict a warm circumstance associated with abundant seismicity. Results reveal a heterogeneous slab ranging from 300 °C to over 900 °C from the Moho to subvolcanic depth. The subduction seismicity corresponds well to the plate interface where dynamic thermal dehydration is focused. The transformation from hydrated basalts to eclogites along the slab facilitates the occurrence of intense earthquakes and slips. Multistage mineralogical metamorphism affects the dynamic stability of megathrusts and favors the generation of active interplate large events. Therefore, slab thermal dehydration plays a greater role than slab temperature condition in influencing the subduction earthquake distribution in warm subduction systems.

Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA): Influences on the Voice Changes and Swallowing Function Disorders.

OBJECTIVE: The aim of this study was to evaluate the influence of transoral endoscopic thyroidectomy vestibular approach (TOETVA) on voice changes and swallowing function disorders. MATERIALS AND METHODS: We retrospectively reviewed 215 patients who underwent thyroid surgery with TOETVA (105 cases, endoscopic group) and open approach (110 cases, open group). Major outcomes, the changes in voice and swallowing function in the 2 groups of patients before and after surgery were analyzed by using both subjective and objective evaluation indexes. Subjective evaluation indexes included the Voice Handicap Index, voice GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) classification, and swallowing impairment score; the objective indicators included the fundamental frequency (F0), fundamental frequency perturbation (jitter), amplitude perturbation (shimmer), and maximum phonation time. RESULTS: In terms of subjective evaluation indexes, there were no significant differences (all P> 0.05) between the groups regarding Voice Handicap Index (1 and 3 mo after surgery) and GRBAS (1 and 3 mo after surgery). The incidence rates of swallowing disorder in the endoscopic group were higher than that in the open group according to the outcomes of swallowing impairment score at 1 and 3 months after surgery (both P< 0.05). In addition, no significant changes in terms of jitter, shimmer, and maximum phonation time in both groups of patients at 1 and 3 months after surgery compared with their preoperative values (all P> 0.05). CONCLUSIONS: Voice and swallowing disorders may occur in some patients, either TOETVA or open thyroid surgery, which in most cases will recover within 3 months after surgery. The time to swallowing function recovery is relatively prolonged in patients following TOETVA, which may be probably associated with neck adhesion and fixation after the operation.

Variation in the thermal and dehydration regime below Central America: Insights for the seismogenic plate interface.

Slow earthquakes predominant in Costa Rica indicate unstable faulting of segmented Central American megathrusts, but the recurrence of episodic tremors and slips reported to precede a giant earthquake remains still enigmatic. The underlying mechanism is related to the variation in the coupling along the heterogeneous subduction interface which is poorly understood. In this study, we used up-to-date 3D thermal modeling to provide insights into the along-strike variation in the thermal state and hydraulic distribution beneath the Central American subduction zone. Our results show that the subducted Cocos Plate is much warmer than previously estimated, and the slab geometry exhibits remarkable perturbations along the trench. We found that the regions of large dehydration rate along the slab are consistent with the seismicity occurrence depth beneath the Moho. Below the Nicoya Peninsula and the Guatemala-Nicaragua segment of megathrusts, fluids derived from subducted slab result in increased pore fluid pressures and subsequent recurrence of slow slip events and regular earthquakes.

Present-Day Tectonic Stress Evolution in Southern Yunnan Based on Focal Mechanisms.

Tectonic extrusion bypassing the eastern Himalayan syntaxis results in a significant increase in regional stress instability and the associated frequent occurrence of earthquakes in southern Yunnan, China. However, the stress field, and the relationship between the focal mechanism of earthquakes and stress evolution in southern Yunnan, remain enigmatic. In this paper, using a modified grid point test method, we calculated the focal mechanism of ML ≥ 2.5 earthquakes in southern Yunnan (22-25° N, 100-104° E) from January 2009 to June 2023. Utilizing the solutions of historical earthquake focal mechanisms, we obtained the present-day regional tectonic stress field in southern Yunnan via inversion. The results indicate complex and diverse seismic focal mechanisms, and the main types of earthquakes are strike-slip events, followed by normal fault and reverse fault events. The orientations of the maximum and minimum principal stress axes rotate in a clockwise direction from northeast to southwest. The internal stress orientation distribution of the rhombic Sichuan-Yunnan block in the study area is consistent, and the block boundary zone is the site where stress deflection occurs, and the regional tectonic stress field is influenced by the interaction among different blocks. The distribution of R-value in the Lamping-Simao block gradually increases from north to south, indicating that the compressive stress required for material transport becomes relatively small. Combined with the geological and tectonic background of the study area, our results suggest that the speed of block movement gradually decreases from north to south; the distribution of R-value in the South China block is significantly smaller than that of the interior of the Sichuan-Yunnan rhombus, and the proportion of compressive stresses is larger, indicating a stronger extrusion in this region, which may be related to the fact that the Sichuan-Yunnan rhombus is strongly resisted by the South China block in the east.