A Bimetallic Nanomodulator to Reverse Immunosuppression via Sonodynamic-Ferroptosis and Lactate Metabolism Modulation.

Triple-negative breast cancer (TNBC) responds poorly to immunotherapy due to insufficient immunogenicity and highly immunosuppressive tumor microenvironment (TME). Herein, an intelligent calcium/cobalt-based nanomodulator (Ca,Co)CO3-LND-TCPP@F127-TA (abbreviated as CCLT@FT) is developed to act as a sonodynamic-ferroptosis inducer and metabolic immunoadjuvant to enhance anti-tumor immunotherapy. More details, simultaneous reactive oxygen species (ROS) generation and glutathione (GSH) depletion can be achieved due to the existence of Co2+/Co3+ redox couple in CCLT@FT. Meanwhile, mitochondrial Ca2+ overload and tetrakis(4-carboxyphenyl) porphyrin (TCPP)-mediated sonodynamic therapy (SDT) further amplify the oxidative stress and promote ferroptosis in tumor cells. More impressively, CCLT@FT can modulate lactate metabolism by doping with cobalt and loading with lonidamine (LND, an inhibitor of MCT4), thereby reversing the high-lactate immunosuppressive TME. Furthermore, the combination with immune checkpoint blockade (ICB) therapy is found to achieve superior anti-tumor immunity, which in turn promotes ferroptosis of tumor cells by downregulating SLC7A11 protein, ultimately creating a "cycle" therapy. Overall, this work demonstrates a novel strategy for enhancing anti-tumor immunotherapy based on a closed-loop enhancement therapeutic route between CCLT@FT inducing ferroptosis/lactate metabolism modulation and ICB therapy, providing an alternative and important reference for effective immunotherapy of TNBC.

Association of Valproic Acid and Its Main Metabolites' Plasma Concentrations with Clinical Outcomes among Epilepsy Patients: A 10-Year Retrospective Study Based on Therapeutic Drug Monitoring.

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 µg/mL) is inadequate for predicting clinical outcomes. Additionally, the relationship between VPA metabolites and clinical outcomes remains unclear. In this retrospective study, 485 Chinese Southern Han epilepsy patients receiving VPA monotherapy were analyzed after reaching steady-state levels. Plasma concentrations of VPA and its five main metabolites were determined by liquid chromatography-mass spectrometry (LC-MS). We assessed the relevance of the recommended therapeutic VPA range for clinical outcomes and explored the association between VPA/metabolites levels and treatment efficacy/adverse effects. Vitro experiments were conducted to assess 4-ene-VPA hepatotoxicity. The therapeutic range of VPA exhibited no significant correlation with clinical outcomes, and plasma concentrations of VPA failed to serve as predictive indicators for treatment response/adverse effects. Treatment responders had higher 2-PGA concentrations (median, 26.39 ng/mL versus 13.68 ng/mL), with a threshold of 36.5 ng/mL for optimal epilepsy treatment. Patients with abnormal liver function had a higher 4-ene-VPA median concentration (6.41 µg/mL versus 4.83 µg/mL), and the ratio of 4-ene-VPA to VPA better predicted VPA-induced hepatotoxicity (area under the curve, 0.718) than 4-ene-VPA concentration. Vitro experiments revealed that 4-ene-VPA was more hepatotoxic than VPA in HepaRG and L02 cell lines. Total plasma VPA concentration does not serve as a predictor of clinical outcomes. 2-PGA concentrations may be associated with efficacy, whereas the ratio of 4-ene-VPA to VPA may be considered a better biomarker (threshold 10.03%) for VPA-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This was the first and largest observational cohort in China to explore the relationship between patients' parent and metabolites concentrations of VPA and clinical outcomes during the maintenance of VPA monotherapy in epileptic patients. This study provided feasible references of VPA for epilepsy clinical treatment with a larger sample of patients compared with previous studies for a more definitive conclusion based on real-world situations. We found two potential biomarkers in predicting efficacy and liver injury, respectively. This breakthrough has the potential to assist in the rational use of VPA.

Improved Patient Adherence to Family-Based Helicobacter pylori Infection Control and Management Strategy in Central China and Its Influencing Factors.

BACKGROUND: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention. MATERIALS AND METHODS: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed. RESULTS: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention.

Family-based Helicobacter pylori infection control and management strategy and screen-and-treat strategy are highly cost-effective in preventing multiple upper gastrointestinal diseases in Chinese population at national level.

BACKGROUND: The overall benefits of the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management (FBCM) and screen-and-treat strategies in preventing multiple upper gastrointestinal diseases at national level in China have not been explored. We investigate the cost-effectiveness of these strategies in the whole Chinese population. MATERIALS AND METHODS: Decision trees and Markov models of H. pylori infection-related non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were developed to simulate the cost-effectiveness of these strategies in the whole 494 million households in China. The main outcomes include cost-effectiveness, life years (LY), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS: When compared with no-screen strategy, both FBCM and screen-and-treat strategies reduced the number of new cases of NUD, PUD, PUD-related deaths, and the prevalence of GC, and cancer-related deaths. The costs saved by these two strategies were $1467 million and $879 million, quality-adjusted life years gained were 227 million and 267 million, and life years gained were 59 million and 69 million, respectively. Cost-effectiveness analysis showed that FBCM strategy costs -$6.46/QALY and -$24.75/LY, and screen-and-treat strategy costs -$3.3/QALY and -$12.71/LY when compared with no-screen strategy. Compared to the FBCM strategy, the screen-and-treat strategy reduced the incidence of H. pylori-related diseases, added 40 million QALYs, and saved 10 million LYs, but at the increased cost of $588 million. Cost-effectiveness analysis showed that screen-and-treat strategy costs $14.88/QALY and $59.5/LY when compared with FBCM strategy. The robustness of the results was also verified. CONCLUSIONS: Both FBCM and screen-and-treat strategies are highly cost-effective in preventing NUD, PUD, and GC than the no-screen strategy in Chinese families at national level. As FBCM strategy is more practical and efficient, it is expected to play a more important role in preventing familial H. pylori infection and also serves as an excellent reference for other highly infected societies.

Lightweight Vehicle Detection Based on Improved YOLOv5s.

A vehicle detection algorithm is an indispensable component of intelligent traffic management and control systems, influencing the efficiency and functionality of the system. In this paper, we propose a lightweight improvement method for the YOLOv5 algorithm based on integrated perceptual attention, with few parameters and high detection accuracy. First, we propose a lightweight module IPA with a Transformer encoder based on integrated perceptual attention, which leads to a reduction in the number of parameters while capturing global dependencies for richer contextual information. Second, we propose a lightweight and efficient multiscale spatial channel reconstruction (MSCCR) module that does not increase parameter and computational complexity and facilitates representative feature learning. Finally, we incorporate the IPA module and the MSCCR module into the YOLOv5s backbone network to reduce model parameters and improve accuracy. The test results show that, compared with the original model, the model parameters decrease by about 9%, the average accuracy (mAP@50) increases by 3.1%, and the FLOPS does not increase.

Straw Incorporation with Exogenous Degrading Bacteria (ZJW-6): An Integrated Greener Approach to Enhance Straw Degradation and Improve Rice Growth.

Rice straw is an agricultural waste, the disposal of which through open burning is an emerging challenge for ecology. Green manufacturing using straw returning provides a more avant-garde technique that is not only an effective management measure to improve soil fertility in agricultural ecosystems but also nurtures environmental stewardship by reducing waste and the carbon footprint. However, fresh straw that is returned to the field cannot be quickly decomposed, and screening microorganisms with the capacity to degrade straw and understanding their mechanism of action is an efficient approach to solve such problems. This study aimed to reveal the potential mechanism of influence exerted by exogenous degradative bacteria (ZJW-6) on the degradation of straw, growth of plants, and soil bacterial community during the process of returning rice straw to the soil. The inoculation with ZJW-6 enhanced the driving force of cellulose degradation. The acceleration of the rate of decomposition of straw releases nutrients that are easily absorbed by rice (Oryza sativa L.), providing favorable conditions for its growth and promoting its growth and development; prolongs the photosynthetic functioning period of leaves; and lays the material foundation for high yields of rice. ZJW-6 not only directly participates in cellulose degradation as degrading bacteria but also induces positive interactions between bacteria and fungi and enriches the microbial taxa that were related to straw degradation, enhancing the rate of rice straw degradation. Taken together, ZJW-6 has important biological potential and should be further studied, which will provide new insights and strategies for the appropriate treatment of rice straw. In the future, this degrading bacteria may provide a better opportunity to manage straw in an ecofriendly manner.

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

Crystal structures of N-terminally truncated telomerase reverse transcriptase from fungi‡.

Telomerase plays critical roles in cellular aging, in the emergence and/or development of cancer, and in the capacity for stem-cell renewal, consists of a catalytic telomerase reverse transcriptase (TERT) and a template-encoding RNA (TER). TERs from diverse organisms contain two conserved structural elements: the template-pseudoknot (T-PK) and a helical three-way junction (TWJ). Species-specific features of the structure and function of telomerase make obtaining a more in-depth understanding of the molecular mechanism of telomerase particularly important. Here, we report the first structural studies of N-terminally truncated TERTs from Candida albicans and Candida tropicalis in apo form and complexed with their respective TWJs in several conformations. We found that Candida TERT proteins perform only one round of telomere addition in the presence or absence of PK/TWJ and display standard reverse transcriptase activity. The C-terminal domain adopts at least two extreme conformations and undergoes conformational interconversion, which regulates the catalytic activity. Most importantly, we identified a conserved tertiary structural motif, called the U-motif, which interacts with the reverse transcriptase domain and is crucial for catalytic activity. Together these results shed new light on the structure and mechanics of fungal TERTs, which show common TERT characteristics, but also display species-specific features.

KAT5 acetylates cGAS to promote innate immune response to DNA virus.

The DNA sensor cGMP-AMP synthase (cGAS) senses cytosolic microbial or self DNA to initiate a MITA/STING-dependent innate immune response. cGAS is regulated by various posttranslational modifications at its C-terminal catalytic domain. Whether and how its N-terminal unstructured domain is regulated by posttranslational modifications remain unknown. We identified the acetyltransferase KAT5 as a positive regulator of cGAS-mediated innate immune signaling. Overexpression of KAT5 potentiated viral-DNA-triggered transcription of downstream antiviral genes, whereas a KAT5 deficiency had the opposite effects. Mice with inactivated Kat5 exhibited lower levels of serum cytokines in response to DNA virus infection, higher viral titers in the brains, and more susceptibility to DNA-virus-induced death. Mechanistically, KAT5 catalyzed acetylation of cGAS at multiple lysine residues in its N-terminal domain, which promoted its DNA-binding ability. Our findings suggest that KAT5-mediated cGAS acetylation at its N terminus is important for efficient innate immune response to DNA virus.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Histone H3K4 methyltransferases SDG25 and ATX1 maintain heat-stress gene expression during recovery in Arabidopsis.

Plants have short-term stress memory that enables them to maintain the expression state of a substantial subset of heat-inducible genes during stress recovery after heat stress. Little is known about the molecular mechanisms controlling stress-responsive gene expression at the recovery stage in plants, however. In this article, we demonstrate that histone H3K4 methyltransferases SDG25 and ATX1 are required for heat-stress tolerance in Arabidopsis. SDG25 and ATX1 are not only important for stress-responsive gene expression during heat stress, but also for maintaining stress-responsive gene expression during stress recovery. A combination of whole-genome bisulfite sequencing, RNA-sequencing and ChIP-qPCR demonstrated that mutations of SDG25 and ATX1 decrease histone H3K4me3 levels, increase DNA cytosine methylation and inhibit the expression of a subset of heat stress-responsive genes during stress recovery in Arabidopsis. ChIP-qPCR results confirm that ATX1 binds to chromatins associated with these target genes. Our results reveal that histone H3K4me3 affects DNA methylation at regions in the loci associated with heat stress-responsive gene expression during stress recovery, providing insights into heat-stress transcriptional memory in plants.

Both family-based Helicobacter pylori infection control and management strategy and screen-and-treat strategy are cost-effective for gastric cancer prevention.

BACKGROUND: Helicobacter pylori (H. pylori) infection and its related diseases are substantial public health burden for highly infected areas. Recently, a novel family-based H. pylori infection control and management (FBCM) strategy is introduced for H. pylori infection prevention and control. However, its cost-effectiveness has not been evaluated. We conducted this health economic evaluation to investigate the cost-effectiveness of FBCM, screen-and-treat, and no-screen strategies in Chinese population. MATERIALS AND METHODS: Cost-effectiveness analysis was performed using decision tree and Markov model. Parameters required for the model were from published literatures and public databases, including health state utility, screening characteristics, treatment effectiveness, and medical costs for the three strategies. Outcomes were cost, quality-adjusted life year (QALY), incremental cost-effectiveness ratio (ICER). Uncertainty analysis was performed to verify the robustness of this model. RESULTS: To prevent gastric cancer in a cohort of 1 million asymptomatic Chinese families, FBCM and screen-and-treat strategies prevented 1010 and 1201 new gastric cancer cases, reduced 2809 and 3339 gastric cancer-related death, and saved 956,971 and 1,137,549 QALYs, respectively, when compared with no-screen strategy. Cost-effectiveness analysis showed that FBCM strategy cost $9.18/QALY, and screen-and-treat strategy cost $12.08/QALY for gastric cancer prevention when compared with no-screen strategy. One-way sensitivity analysis revealed that screening from younger age by both strategies are more cost-effective. When compared with FBCM strategy, screen-and-treat strategy saved 5.98% gastric cancer cases and 5.78% of gastric cancer deaths, but costed $9348 to reduce a gastric cancer case. Results are not sensitive to any variables, and probabilistic sensitivity analysis confirmed robustness of the results. CONCLUSIONS: Both FBCM and screen-and-treat strategies are cost-effective for gastric cancer prevention compared with no-screen strategy. Since FBCM is more practical and convenient, it may be an efficient and excellent cost-effective strategy for gastric cancer prevention in H. pylori and gastric cancer prevalent areas.

Rabeprazole plus amoxicillin dual therapy is equally effective to bismuth-containing quadruple therapy for Helicobacter pylori eradication in central China: A single-center, prospective, open-label, randomized-controlled trial.

BACKGROUND: Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High-dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first-line therapy for H. pylori eradication, and factors that affect the curing rate. METHODS: This is a single-center, prospective, open-label, randomized-controlled trial. Naive patients (n=292) were randomly treated with bismuth-containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13 C-urea breath test. RESULTS: In per-protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention-to-treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group. CONCLUSIONS: Rabeprazole-amoxicillin dual therapy is equally effective to the bismuth-containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non-smoking condition, which deserves future stratified analysis for refinement and optimization.

Mitigating nitrite accumulation during S0-based autotrophic denitrification: Balancing nitrate-nitrite reduction rate with thiosulfate as external electron donor.

This study was carried out to determine the effect of influent nitrate loading on nitrite accumulation during elemental-sulfur based denitrification process, and proposed to enhance the nitrogen removal efficiency by mitigating nitrite accumulation with thiosulfate as external electron donor. Along with increasing the nitrate influent loading (from 0.09 kg N/m3/d to 1.73 kg N/m3/d) by shortening the empty bed contact time (EBCT) (from 5 h to 0.25 h), the nitrate removal loading increased from 0.08 to 0.83 kg N/m3/d. Meanwhile, the raise of the nitrate influent loading obviously aggravated the nitrite accumulation. Herein, nitrite began to accumulate since the nitrate influent loading was over 0.86 kg N/m3/d, and a maximum nitrite accumulation of 2.39 mg/L was observed under the 0.25 h of EBCT and 15 mg/L of nitrate influent concentration condition. Thiosulfate was used as the external electron donor to accelerate the nitrite reduction rate in order to mitigate the nitrite accumulation. As a result, the nitrite accumulation significantly decreased from 2.39 mg/L to 0.17 mg/L with the thiosulfate dosage of 13.36 mg/L. However, the nitrite accumulation bounced with the on-going increase of the thiosulfate dosage, indicating that the nitrate reduction rate and nitrite reduction rate were accelerated alternatively. After dosing thiosulfate, the relative abundances of sulfurimonas and ferritrophicum grew up significantly.

Benefits of step-by-step debulking microwave ablation for huge unresectable hepatocellular carcinoma patients after transcatheter arterial chemoembolization refractoriness.

OBJECTIVES: To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (≥10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness. METHODS: This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-by-step debulking MWA (n = 52) or continued TACE (n = 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group. RESULTS: Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both p < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure. CONCLUSION: Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. Key PointThe debulking MWA therapy provides significantly longer OS and PFS than continued TACE for patients with huge unresectable HCCs after TACE-refractory, especially with complete tumor ablation.The most common complications were fever (48.1%) and pain (46.2%) in the MWA group. Two major complications (abdominal infection) were recorded in the MWA group, which recovered after symptomatic treatment.During the course of repeated MWAs, liver hyperplasia appeared mainly after the second MWA procedure and the average maximum increased RLV/TLV rate was 16.3%±12.7%.

Protein kinases Elm1 and Sak1 of Saccharomyces cerevisiae exerted different functions under high-glucose and heat shock stresses.

Phosphorylation catalyzed by protein kinases is the most common and important regulatory pathway in the adaptive physiological responses to the changes in nutrition and environment of yeast. This study focused on the functions of Elm1, Sak1, and Tos3, which are three upstream protein kinases of Snf1 in Saccharomyces cerevisiae, in response to high-glucose and heat shock stresses. Results suggested that changing the gene dosage of ELM1/SAK1/TOS3 had different effects under high-glucose and heat shock stresses. ELM1 and SAK1 overexpressions could enhance the tolerance of S. cerevisiae to high-glucose and heat shock stresses, respectively. Nevertheless, the overexpression of TOS3 decreased the tolerance to high-glucose stress, and a native level of Tos3 was important for the normal adaptation to heat shock condition. The overexpression of ELM1 increased the accumulation of trehalose and ergosterol and altered the composition of fatty acids with altered gene expressions involved in the metabolism of three metabolites. Enhanced resistance to heat shock stress in SAK1 overexpression might be related to the enhanced accumulation of trehalose and ergosterol and upregulated transcription of genes related to the metabolism of trehalose and ergosterol. Furthermore, Elm1 might regulate the metabolism of trehalose, ergosterol, and fatty acids in a Snf1-independent form under high-glucose stress. A Snf1-independent pathway might be involved in the regulation of trehalose metabolism by Sak1 under heat shock condition. However, Sak1 and Snf1 may have an indirect relationship in the regulation of ergosterol synthesis. KEY POINTS: • Altering the gene dosage of ELM1/SAK1/TOS3 had different effects on stress responses • Elm1 regulated high-glucose response in a Snf1-independent manner • Sak1 and Snf1 had an indirect relationship in the regulation of heat shock response.

QCW surface-pumped cryogenically cooled single-slab laser with 1 kW level at 946 nm.

We present a kilowatt-level quasi-continuous-wave (QCW) cryogenically cooled 946-nm slab laser oscillator for the first time, to the best of our knowledge. The laser system is based on a double-face-pumped large-size single-slab Nd:YAG design, delivering a record-high average power of 1.06 kW without additional amplification. This laser oscillator operates at repetition rate of 400 Hz with a pulse duration of 175 µs, resulting in a single pulse energy of 2.65 J. To the best of our knowledge, these results represent the highest output power and pulse energy for any all-solid-state 946-nm laser ever reported to date. Our scheme paves a new path for the development of the compact high-power solid-state 946-nm laser.

Research on Cyanobacterial-Bloom Detection Based on Multispectral Imaging and Deep-Learning Method.

Frequent outbreaks of cyanobacterial blooms have become one of the most challenging water ecosystem issues and a critical concern in environmental protection. To overcome the poor stability of traditional detection algorithms, this paper proposes a method for detecting cyanobacterial blooms based on a deep-learning algorithm. An improved vegetation-index method based on a multispectral image taken by an Unmanned Aerial Vehicle (UAV) was adopted to extract inconspicuous spectral features of cyanobacterial blooms. To enhance the recognition accuracy of cyanobacterial blooms in complex scenes with noise such as reflections and shadows, an improved transformer model based on a feature-enhancement module and pixel-correction fusion was employed. The algorithm proposed in this paper was implemented in several rivers in China, achieving a detection accuracy of cyanobacterial blooms of more than 85%. The estimate of the proportion of the algae bloom contamination area and the severity of pollution were basically accurate. This paper can lay a foundation for ecological and environmental departments for the effective prevention and control of cyanobacterial blooms.

Polyvinyl acetate-based soil stabilization for rock slope ecological restoration.

External-soil spray seeding (ESSS) is a method often used for the ecological restoration of bare rock slopes. However, the direct use of ESSS is normally less satisfactory due to the erosion of sprayed soil and low survival rate of the plants on rock slopes. This study proposes a novel approach to addressing this issue through the combined use of ESSS with polyvinyl acetate (PVA) based soil stabilization. The PVA solutions are added to the soil to stabilize soil and improve soil strength while possessing high water and nutrient retention favorable for plant growth. A series of experimental tests on the mechanical properties, water stability, erosion resistance, water retention, and plant growth of the PVA-stabilized soil were conducted to assess the efficacy of the proposed method. The results showed that the proposed method could be promising for rock slope ecological restoration. A proper curing time (e.g., >3 days) was required to achieve beneficial effects of PVA on the soil properties. A shorter curing time would otherwise result in the decrease in the strength with the increased PVA content. It was found that the optimum PVA content was 3% for achieving the maximum water stability, erosion resistance, water retention, and plant growth. The cohesion increased by up to 50% and the internal friction angle increased by 3.5° compared to the natural soil. The disintegration rate of the stabilized soil was generally < 3e-3%/min. The maximum reduction in erosion was up to 83% when the PVA content ≥3%. The mechanisms behind the findings are also discussed.

UBA domain protein SUF1 interacts with NatA-complex subunit NAA15 to regulate thermotolerance in Arabidopsis.

During recovery from heat stress, plants clear away the heat-stress-induced misfolded proteins through the ubiquitin-proteasome system (UPS). In the UPS, the recognition of substrate proteins by E3 ligase can be regulated by the N-terminal acetyltransferase A (NatA) complex. Here, we determined that Arabidopsis STRESS-RELATED UBIQUITIN-ASSOCIATED-DOMAIN PROTEIN FACTOR 1 (SUF1) interacts with the NatA complex core subunit NAA15 and positively regulates NAA15. The suf1 and naa15 mutants are sensitive to heat stress; the NatA substrate N SNC1 is stabilized in suf1 mutant plants during heat stress recovery. Therefore, SUF1 and its interactor NAA15 play important roles in basal thermotolerance in Arabidopsis.