Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat.

OBJECTIVE: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). MATERIALS AND METHODS: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. RESULTS: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). CONCLUSIONS: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

Fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy.

Chemotherapy is one of the conventional treatments for cancer in clinical practice. However, poor delivery efficiency, systemic toxicity, and the lack of pharmacokinetic monitoring during treatment are the critical limitations of current chemotherapy. Herein, we reported a brand-new antitumor drug delivery strategy that harnesses an optical fiber endoscopically therapeutic probe. The fiber probe carries photosensitizers in the fiber core and antitumor agents on the fiber surface mediated by a temperature-responsive hydrogel film, giving rise to an activable photothermal-chemotherapy that orchestrates the localized hyperthermia and thermal-stimuli drug release to the tumor lesion. Furthermore, the dynamical drug release and in-situ temperature can be real-time supervised through the built-in fiber sensors, including the reflective Mach-Zehnder interferometer and fiber Bragg grating, to visualize the therapy process and thus improve the safety of treatment. Compared with conventional methods, the fiber-optic drug delivery can adequately take advantage of the chemotherapeutics through collaboratively recruiting the photoheating-mediated enhanced permeability and the hydrogel particle-assisted high drug retention, shedding new light on a "central-to-peripheral" drug pervasion and retention mechanism to destroy tumors completely. The fiber-optic chemotherapy strategy incorporates precise drug delivery, accurate controllability of drug release, high drug permeability and retention in tumor, low off-target rate, and real-time drug release and temperature feedback, performing a straightforward and precise photothermal-chemotherapy pathway. More than that, the proposed strategy holds tremendous promise to provide a revolutionized on-demand drug delivery platform for the highly efficient evaluation and screening of antitumor pharmaceuticals.

Postoperative clearance of high-risk human papillomavirus for patients with high-grade squamous intraepithelial lesion: Conization versus hysterectomy.

To compare the clearance rate of high-risk human papillomavirus (HR-HPV) in patients with high-grade squamous intraepithelial lesion (HSIL) after 2 different treatments (conization vs hysterectomy), and investigate the influencing factors. A retrospective cohort was established in HSIL patients with HR-HPV infection treated with conization or hysterectomy from July 2020 to May 2022. Age matching (1:1) was conducted between conization group and hysterectomy group. Chi-square test and t-test were employed to compare baseline and clinical characteristics between the 2 groups (conization vs hysterectomy). In addition, univariate and multivariate logistic regression analyses were conducted to compare the influencing factors for HR-HPV clearance at 6 months after surgery. The HR-HPV clearance rates at 6 months were 70.6% and 73.8% in conization group and hysterectomy group in the matched groups, respectively (P = .755). Similarly, at 12 months, the clearance rates were 78.6% and 76.5% in the matched groups, respectively (P = .844). Considering different age groups among all patients, the HR-HPV clearance rates were 81.8%, 72.9%, 73.5%, and 53.6% in the 20 to 30-year, 31 to 40-year, 41 to 50-year and 51 to 60-year groups at 6 months, respectively, and the clearance rates were 87.5%, 80.6%, 84.5% and 52.9% at 12 months, respectively. For HSIL, the postoperative HPV clearance rates were similar between the 2 groups (conization vs hysterectomy), conization is enough to resect the lesion and eliminate HPV. In addition, we should pay attention to the postoperative HR-HPV status in the older population of the 2 groups.

Construction of a Prognostic Nomogram for Major Amputation Within 30 Days Postrevascularization in Patients With Acute Lower Limb Ischemia Based on 2D Perfusion Parameters.

PURPOSE: The purpose of the study is to develop a prediction model for major amputation (MA) within 30 days after arterial revascularization in patients with acute lower limb ischemia (ALLI) using 2-dimensional (2D) perfusion imaging parameters. MATERIALS AND METHODS: A retrospective study was performed in ALLI patients undergoing arterial revascularization between October 2015 and May 2022. Patients were randomly assigned into training and validation cohorts in a ratio of 7:3. Variables were selected using univariate and multivariate logistic regression. A nomogram for the MA risk within 30 days after arterial revascularization in ALLI patients was created. Its discrimination, calibration, and clinical effectiveness were reported. RESULTS: A total of 310 ALLI patients (326 limbs) were included. The MA rate within 30 days after arterial revascularization was 11.6%. Skin speckle, myoglobin, and time-to-peak were independent risk factors, while atrial fibrillation was a protective factor (all p<0.05). The nomogram predicted 30-day MA with satisfactory discriminative ability. The integrated discrimination improvement was 0.279 and 0.379 for the training and validation cohorts, respectively (both p<0.001). Calibration curves were close to the standard curve. The decision curve analysis demonstrated net benefits. CONCLUSION: This 2D perfusion imaging parameter-based nomogram could accurately predict the risk of MA within 30 days postrevascularization in ALLI patients. CLINICAL IMPACT: This study introduces a novel nomogram based on 2-dimensional (2D) perfusion imaging that can significantly advance the prognosis prediction in ALLI patients. By calculating the risk of major amputation within 30 days postrevascularization, this nomogram offers an accurate predictive tool and can lead to more informed decision-making on patient management. The innovative aspect of this research lies in its utilization of 2D perfusion parameters, a novel approach that enhances risk assessment accuracy in ALLI patients. This nomogram represents a significant step toward risk stratification and can guide future research for appropriate management on ALLI patients with different risk profiles.

The Accumulation of Abscisic Acid Increases the Innate Pool of Soluble Phenolics through Polyamine Metabolism in Rice Seedlings under Hexavalent Chromium Stress.

Potential toxic element (PTE) pollution has emerged as a significant environmental and social concern in global agriculture. Chromium (Cr) occurs in different oxidation states naturally, among them Cr(VI), which is highly toxic. This study carried out biochemical and molecular tests to elucidate the accumulation of total soluble phenolics (TSPs) in rice plants exposed to Cr(VI) at 2.0, 8.0, and 16.0 mg Cr/L, emphasizing the interaction between polyamines (PAs) and abscisic acid (ABA). The results revealed significant Cr accumulation in different tissues of rice plants, which hindered their growth. Cr(VI) exposure increased the ABA concentration, with higher levels detected in the shoots than in the roots. The TSP concentration in rice tissues showed a positive relationship with the supplied concentrations of Cr(VI). The measured PAs, including spermine (Spm), putrescine (Put), and spermidine (Spd), exhibited varied responses to Cr(VI) stress, with only Spm concentration increasing with Cr(VI) concentrations. Real-time qRT-PCR showed PAs and ABA synthesis-associated genes such as OsADC1, OsAIH, OsCPA1, and OsCPA4 were significantly up-regulated in shoot of rice plants treated with Cr(VI). These genes are associated with the second pathway of Put synthesis, originating from Arg. Almost all genes activated in the Met pathway were significantly up-regulated as well. Moreover, the genes involved in the interconversion among the three species of PAs exhibited completely different responses to Cr(VI) exposure. Overall, the biochemical analysis and gene expression data indicate that the interaction between ABA and Spm is likely to enhance the TSP levels in rice plants subjected to Cr(VI) toxicity.

Elevated triglyceride-glucose index associated with increased risk of diabetes in non-obese young adults: a longitudinal retrospective cohort study from multiple Asian countries.

Objective: Previous studies have confirmed a positive correlation between the Triglyceride-Glucose (TyG) index and future risk of diabetes. However, evidence of this association in non-obese young populations remains limited. This study aims to investigate the relationship between the TyG index and the future risk of diabetes among non-obese young adults. Methods: This retrospective cohort study included 113,509 non-obese young adults from China and 9,549 from Japan. The mean age was 35.73 ± 6.38 years, and 56,469 participants (45.89%) were male. The median follow-up duration was 3.38 years. The association between baseline TyG index and risk of diabetes was examined using Cox proportional hazards regression models. Non-linear relationships between the TyG index and risk of diabetes were identified using cubic splines and smoothed curve fitting in the Cox models. Sensitivity and subgroup analyses were also conducted. Results: After adjusting for covariates, the results indicated a positive correlation between the TyG index and risk of diabetes in non-obese young adults (HR=3.57, 95% CI: 2.92-4.36, P<0.0001). A non-linear relationship was observed with an inflection point at 7.3. The HR to the right of this inflection point was 3.70 (95% CI: 3.02-4.52, P<0.0001), while to the left, it was 0.34 (95% CI: 0.06-1.88, P=0.2161). The robustness of our findings was confirmed through a series of sensitivity analyses and subgroup analyses. Conclusion: This study reveals a positive and non-linear association between the TyG index and risk of diabetes among non-obese young adults. Interventions aimed at reducing the TyG index by lowering triglycerides or fasting glucose levels could substantially decrease the future likelihood of developing diabetes in this population.

Oxygen-bridging Fe, Co dual-metal dimers boost reversible oxygen electrocatalysis for rechargeable Zn-air batteries.

Rechargeable zinc-air batteries (ZABs) are regarded as a remarkably promising alternative to current lithium-ion batteries, addressing the requirements for large-scale high-energy storage. Nevertheless, the sluggish kinetics involving oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) hamper the widespread application of ZABs, necessitating the development of high-efficiency and durable bifunctional electrocatalysts. Here, we report oxygen atom-bridged Fe, Co dual-metal dimers (FeOCo-SAD), in which the active site Fe-O-Co-N6 moiety boosts exceptional reversible activity toward ORR and OER in alkaline electrolytes. Specifically, FeOCo-SAD achieves a half-wave potential (E1/2) of 0.87 V for ORR and an overpotential of 310 mV at a current density of 10 mA cm-2 for OER, with a potential gap (ΔE) of only 0.67 V. Meanwhile, FeOCo-SAD manifests high performance with a peak power density of 241.24 mW cm-2 in realistic rechargeable ZABs. Theoretical calculations demonstrate that the introduction of an oxygen bridge in the Fe, Co dimer induced charge spatial redistribution around Fe and Co atoms. This enhances the activation of oxygen and optimizes the adsorption/desorption dynamics of reaction intermediates. Consequently, energy barriers are effectively reduced, leading to a strong promotion of intrinsic activity toward ORR and OER. This work suggests that oxygen-bridging dual-metal dimers offer promising prospects for significantly enhancing the performance of reversible oxygen electrocatalysis and for creating innovative catalysts that exhibit synergistic effects and electronic states.

Machine learning-based decision support model for selecting intra-arterial therapies for unresectable hepatocellular carcinoma: A national real-world evidence-based study.

IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.

Feasibility study of focused ultrasound in the treatment of vulvar low-grade squamous intraepithelial lesions with persistent symptoms.

OBJECTIVE: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms. METHODS: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy. RESULTS: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period. CONCLUSION: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.

Application of catalytic technology based on the piezoelectric effect in wastewater purification.

The demands of human life and industrial activities result in a significant influx of toxic contaminants into aquatic ecosystems. In particular, organic pollutants such as antibiotics and dye molecules, bacteria, and heavy metal ions are represented, posing a severe risk to the health and continued existence of living organisms. The method of removing pollutants from water bodies by utilizing the principle of the piezoelectric effect in combination with chemical catalytic processes is superior to other wastewater purification technologies because it can collect water energy, mechanical energy, etc. to achieve cleanliness and high removal efficiency. Herein, we briefly introduced the piezoelectric mechanisms and then reviewed the latest advances in the design and synthesis of piezoelectric materials, followed by a summary of applications based on the principle of piezoelectric effect to degrade pollutants in water for wastewater purification. Moreover, water purification technologies incorporating the piezoelectric effect, including piezoelectric effect-assisted membrane filtration, activation of persulfate, and battery electrocatalysis are elaborated. Finally, future challenges and research directions for the piezoelectric effect are proposed.

Hepatic artery infusion chemotherapy combined with camrelizumab plus rivoceranib for hepatocellular carcinoma with portal vein tumor thrombosis: a multicenter propensity score-matching analysis.

BACKGROUND: Portal vein tumor thrombosis (PVTT) signifies late-stage hepatocellular carcinoma (HCC) with high-risk progression and poor prognosis. As a standard treatment, sorafenib monotherapy has limited the efficacy in managing HCC with PVTT. Currently, both hepatic arterial infusion chemotherapy (HAIC) and the combination of camrelizumab and rivoceranib have shown favorable survival benefits for advanced HCC, surpassing the standard sorafenib treatment. In this study, we investigate the safety and efficacy of HAIC combined with camrelizumab and rivoceranib in treating HCC patients with PVTT. METHODS: From January 2020 to December 2021, HCC patients with PVTT, who received either a triple regime of HAIC combined with camrelizumab and rivoceranib or a dual regime of camrelizumab and rivoceranib as their first-line treatment, were reviewed for eligibility at four hospital centers in China. To balance any intergroup differences, propensity score matching (PSM) was applied. The aim of this study is to compare the efficacy of the dual and triple combination treatment regimens based on survival prognosis and tumor response and evaluate the safety based on the occurrence of adverse reactions. RESULT: In this study, a total of 411 patients who received either the triple treatment regime (HAIC combined with camrelizumab plus rivoceranib, referred to as the HAICCR group, n = 292) or the dual treatment regime (camrelizumab combined with rivoceranib, referred to as the CR group, n = 119) between January 2020 and December 2021 were included. The results showed that the HAICCR group exhibited significantly better overall survival (mOS: 19.60 months vs. 11.50 months, p < 0.0001) and progression-free survival (mPFS: 10.0 months vs. 5.6 months, p < 0.0001) compared to the CR group in the overall cohort. Moreover, the HAICCR group also had a significantly higher ORR (objective response rate, 55.5% vs. 42.0%, p = 0.013) and DCR (disease control rate, 89.0% vs. 79.0%) compared to the CR group. After PSM, a final matched cohort of 83 pairs was obtained, and the survival benefits were consistent in this cohort as well (mOS: 18.70 months vs. 11.0 months, p < 0.0001; mPFS: 10.0 months vs. 5.6 months, p < 0.0001). However, there was no significant difference in the ORR between the triple and dual combination regimes. Univariate and multivariate analysis showed that CTP (Child-Turcotte-Pugh) stage, ALBI (albumin-bilirubin index) grade, tumor number, and treatment regime were significant risk factors affecting overall survival, while AFP (α-fetoprotein) level, tumor number, metastasis, and treatment regime were significant risk factors affecting progression-free survival. As for safety, hypertension and hand-foot syndrome were the two most common adverse reactions in both groups, with no significant difference in the occurrence of adverse reactions between the two groups (p < 0.05). CONCLUSION: In the context of advanced HCC patients with PVTT, the combination regime of HAIC and camrelizumab plus rivoceranib demonstrates more excellent capacity for prolonging survival and offers a well-tolerated safety compared to the CR dual therapy approach. This triple regime represents a therapeutic modality of broad prospects and vast potential for HCC patients with PVTT.

Research progress on the origin, fate, impacts and harm of microplastics and antibiotic resistance genes in wastewater treatment plants.

Previous studies reported microplastics (MPs), antibiotics, and antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs). There is still a lack of research progress on the origin, fate, impact and hazards of MPs and ARGs in WWTPs. This paper fills a gap in this regard. In our search, we used "microplastics", "antibiotic resistance genes", and "wastewater treatment plant" as topic terms in Web of Science, checking the returned results for relevance by examining paper titles and abstracts. This study mainly explores the following points: (1) the origins and fate of MPs, antibiotics and ARGs in WWTPs; (2) the mechanisms of action of MPs, antibiotics and ARGs in sludge biochemical pools; (3) the impacts of MPs in WWTPs and the spread of ARGs; (4) and the harm inflicted by MPs and ARGs on the environment and human body. Contaminants in sewage sludge such as MPs, ARGs, and antibiotic-resistant bacteria enter the soil and water. Contaminants can travel through the food chain and thus reach humans, leading to increased illness, hospitalization, and even mortality. This study will enhance our understanding of the mechanisms of action among MPs, antibiotics, ARGs, and the harm they inflict on the human body.

Cytosolic DNA initiates a vicious circle of aging-related endothelial inflammation and mitochondrial dysfunction via STING: the inhibitory effect of Cilostazol.

Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.

Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release.

The development of artificial receptors that combine ultrahigh-affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high binding affinity can resist unwanted dissociation induced by dilution effect and complex interferents within physiological environments. On the other hand, stimulus-responsive release of the guest is essential for precisely activating its function. In this context, we expanded hydrophobic cavity surface of a hypoxia-responsive azocalix[4]arene, affording Naph-SAC4A. This modification significantly enhanced its aqueous binding affinity to 1013 M-1, akin to the naturally occurring strongest recognition pair, biotin/(strept-)avidin. Consequently, Naph-SAC4A emerges as the first artificial receptor to simultaneously integrate ultrahigh recognition affinity and actively controllable release. The markedly enhanced affinity not only improved Naph-SAC4A's sensitivity in detecting rocuronium bromide in serum, but also refined the precision of hypoxia-responsive doxorubicin delivery at the cellular level, demonstrating its immense potential for diverse practical applications.

Elucidating the intricacies of the H2S signaling pathway in gasotransmitters: Highlighting the regulation of plant thiocyanate detoxification pathways.

In recent decades, there has been increasing interest in elucidating the role of sulfur-containing compounds in plant metabolism, particularly emphasizing their function as signaling molecules. Among these, thiocyanate (SCN-), a compound imbued with sulfur and nitrogen, has emerged as a significant environmental contaminant frequently detected in irrigation water. This compound is known for its potential to adversely impact plant growth and agricultural yield. Although adopting exogenous SCN- as a nitrogen source in plant cells has been the subject of thorough investigation, the fate of sulfur resulting from the assimilation of exogenous SCN- has not been fully explored. There is burgeoning curiosity in probing the fate of SCN- within plant systems, especially considering the possible generation of the gaseous signaling molecule, hydrogen sulfide (H2S) during the metabolism of SCN-. Notably, the endogenous synthesis of H2S occurs predominantly within chloroplasts, the cytosol, and mitochondria. In contrast, the production of H2S following the assimilation of exogenous SCN- is explicitly confined to chloroplasts and mitochondria. This phenomenon indicates complex interplay and communication among various subcellular organelles, influencing signal transduction and other vital physiological processes. This review, augmented by a small-scale experimental study, endeavors to provide insights into the functional characteristics of H2S signaling in plants subjected to SCN--stress. Furthermore, a comparative analysis of the occurrence and trajectory of endogenous H2S and H2S derived from SCN--assimilation within plant organisms was performed, providing a focused lens for a comprehensive examination of the multifaceted roles of H2S in rice plants. By delving into these dimensions, our objective is to enhance the understanding of the regulatory mechanisms employed by the gasotransmitter H2S in plant adaptations and responses to SCN--stress, yielding invaluable insights into strategies for plant resilience and adaptive capabilities.

Efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD1 therapy versus HAIC monotherapy for advanced hepatocellular carcinoma: A multicenter propensity score matching analysis.

PURPOSE: To investigate the clinical efficacy and safety of combination therapy of hepatic arterial infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) therapy in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective clinical research, from March 2018 to December 2019, 1158 HCC patients categorized as BCLC stage C were reviewed for eligibility. We utilized propensity score matching (PSM) to mitigate initial disparities between the groups. The evaluation of the best tumor response was conducted in accordance with mRECIST 1.1 criteria. The difference in survival outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) between groups were compared. RESULTS: Following the eligibility review, 453 patients underwent a combined treatment of HAIC with PD1 inhibitors (HAIC-PD1 group), while 221 patients received HAIC monotherapy (HAIC group) met the inclusion criteria and were finally enrolled in this study. In the entire cohort, the HAIC-PD1 group exhibited significantly prolonged overall survival (median overall survival: 40.4 months vs. 9.7 months, p < 0.001) and progression-free survival (median progression-free survival: 22.1 months vs. 5.8 months, p < 0.001). By propensity score, patients were matched according to baseline differences, resulting in all 442 patients in group HAIC-PD1 (n = 221) and group HAIC (n = 221). After PSM adjustment, as well, the survival of the HAIC-PD1 group was still distinctly longer than the HAIC group (median overall survival time, 40.4 months vs 9.7 months, p < 0.001; median progression-free survival, 22.1 months vs 5.7 months, p < 0.001). Univariate and multivariable analysis demonstrated that AFP level, metastasis, and therapeutic schedule were independent predictive factors for overall survival. CONCLUSION: The combination therapy of HAIC and PD1 inhibitors successfully extended OS to advanced HCC patients and could be a better choice than HAIC monotherapy.

Prognosis prediction and risk stratification of transarterial chemoembolization or intraarterial chemotherapy for unresectable hepatocellular carcinoma based on machine learning.

OBJECTIVE: To develop and validate a risk scoring scale model (RSSM) for stratifying prognostic risk after intra-arterial therapies (IATs) for hepatocellular carcinoma (HCC). METHODS: Between February 2014 and October 2022, 2338 patients with HCC who underwent initial IATs were consecutively enrolled. These patients were divided into training datasets (TD, n = 1700), internal validation datasets (ITD, n = 428), and external validation datasets (ETD, n = 200). Five-years death was used to predict outcome. Thirty-four clinical information were input and five supervised machine learning (ML) algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBT), and Random Forest (RF), were compared using the areas under the receiver operating characteristic (AUC) with DeLong test. The variables with top important ML scores were used to build the RSSM by stepwise Cox regression. RESULTS: The CatBoost model achieved the best discrimination when 12 top variables were input, with the AUC of 0.851 (95% confidence intervals (CI), 0.833-0.868) for TD, 0.817 (95%CI, 0.759-0.857) for ITD, and 0.791 (95%CI, 0.748-0.834) for ETD. The RSSM was developed based on the immune checkpoint inhibitors (ICI) (hazard ratios (HR), 0.678; 95%CI 0.549, 0.837), tyrosine kinase inhibitors (TKI) (HR, 0.702; 95%CI 0.605, 0.814), local therapy (HR, 0.104; 95%CI 0.014, 0.747), response to the first IAT (HR, 4.221; 95%CI 2.229, 7.994), tumor size (HR, 1.054; 95%CI 1.038, 1.070), and BCLC grade (HR, 2.375; 95%CI 1.950, 2.894). Kaplan-Meier analysis confirmed the role of RSSM in risk stratification (p < 0.001). CONCLUSIONS: The RSSM can stratify accurately prognostic risk for HCC patients received IAT. On the basis, an online calculator permits easy implementation of this model. CLINICAL RELEVANCE STATEMENT: The risk scoring scale model could be easily implemented for physicians to stratify risk and predict prognosis quickly and accurately, thereby serving as a more favorable tool to strengthen individualized intra-arterial therapies and management in patients with unresectable hepatocellular carcinoma. KEY POINTS: • The Categorical Gradient Boosting (CatBoost) algorithm achieved the optimal and robust predictive ability (AUC, 0.851 (95%CI, 0.833-0.868) in training datasets, 0.817 (95%CI, 0.759-0.857) in internal validation datasets, and 0.791 (95%CI, 0.748-0.834) in external validation datasets) for prediction of 5-years death of hepatocellular carcinoma (HCC) after intra-arterial therapies (IATs) among five machine learning models. • We used the SHapley Additive exPlanations algorithms to explain the CatBoost model so as to resolve the black boxes of machine learning principles. • A simpler restricted variable, risk scoring scale model (RSSM), derived by stepwise Cox regression for risk stratification after intra-arterial therapies for hepatocellular carcinoma, provides the potential forewarning to adopt combination strategies for high-risk patients.

Boron deficiency energizes cyanide uptake and assimilation through activating plasma membrane H+-ATPase in rice plants.

The effect of boron (B) deficiency on mediating the contribution of H+-ATPase in the uptake and assimilation of exogenous cyanide (CN-) is investigated. Under CN- treatments, rice seedlings with B-deficient (-B) conditions exhibited significantly higher CN- uptake and assimilation rates than B-supplemented (+B) seedlings, whereas NH4+ uptake and assimilation rates were slightly higher in -B rice seedlings than in +B. In this connection, the expression pattern of genes encoding ß-CAS, ST, and H+-ATPase was assessed to unravel their role in the current scenario. The abundances of three ß-CAS isogenes (OsCYS-D1, OsCYS-D2, and OsCYS-C1) in rice tissues are upregulated from both "CN--B" and "CN-+B" treatments, however, only OsCYS-C1 in roots from the "CN--B" treatments was significantly upregulated than "CN-+B" treatments. Expression patterns of ST-related genes (OsStr9, OsStr22, and OsStr23) are tissue specific, in which significantly higher upregulation of ST-related genes was observed in shoots from "CN--B" treatments than "CN-+B" treatments. Expression pattern of 7 selected H+-ATPase isogenes, OsA1, OSA2, OsA3, OsA4, OsA7, OsA8, and OsA9 are quite tissue specific between "CN-+B" and "CN--B" treatments. Among these, OsA4 and OsA7 genes were highly activated in the uptake and assimilation of exogenous CN- in -B nutrient solution. These results indicated that B deficiency disturbs the pattern of N cycles in CN--treated rice seedlings, where activation of ST during CN- assimilation decreases the flux of the innate pool of NH4+ produced from CN- assimilation by the ß-CAS pathway in plants. Collectively, the B deficiency increased the uptake and assimilation of exogenous CN- through activating H+-ATPase.

Boron deficiency decreased the root activity of Ga-exposed rice seedlings by reducing iron accumulation and increasing Ga in iron plaque.

Gallium (Ga) is an emerging chemical pollutant chiefly associated with high-tech industries. Boron (B) alleviates the negative effects of toxic elements on plant growth. Thereby, the effects of B fertilization on Ga toxicity in rice seedlings was studied to clarify the role of iron plaque in the distribution of Ga, Fe, and B in Ga-treated rice seedlings in the presence or absence of B. Gallium exposure significantly reduced the biomass of rice seedlings. Boron deficiency induced a significant change in the distribution of B in Ga-treated rice seedlings compared with "Ga+B" treatments. Accumulation of Ga in roots, dithionite-citrate-bicarbonate (DCB) extracts, and shoots showed a dose-dependent manner from both +B and -B rice seedlings. Boron nutrition levels affect the distribution of Fe in roots, DCB extracts, and shoots, in which DCB-extractable Fe was significantly decreased from "Ga-B" treatments compared with "Ga+B" treatments. Root activity was significantly decreased in both Ga-exposed rice seedlings; however, B-deficient seedlings showed a severe reduction than +B rice seedlings. These results reveal that Fe plaque might be a temporary sink for B accumulation when plants are grown with proper B, wherein the re-utilization of DCB-extractable B stored in Fe plaque is mandatory for plant growth under B deficiency. Correlation analysis revealed that B deficiency decreased the root activity of Ga-exposed rice seedlings by reducing DCB-extractable Fe and increasing DCB-extractable Ga in Fe plaque. This study enhances our understanding of how B nutritional levels affect Ga toxicity in rice plants.