Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable esophageal squamous cell carcinoma: A pooled analysis of randomized clinical trials.

BACKGROUND: The comparison of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) for locally advanced esophageal squamous cell carcinoma (ESCC) remains inconclusive, and the optimal regimen is still under investigation. METHODS: Prospective randomized clinical trials were systematically searched in electronic databases from inception to Oct 2023. A graphical reconstructive algorithm was employed to extract time-to-event outcomes from Kaplan-Meier curves presented in the original studies. Using reconstructed individual patient data, summary overall survival (OS) and disease progression-free survival (DFS) for nCRT versus nCT, primarily doublet chemotherapy were recalculated. Hazard Ratios (HRs) of OS and DFS reported were also pooled by the fixed-effects model. RESULTS: A total of 6 randomized clinical trials comprising 1162 patients were included in our analysis. In the individual patient data (IPD) pooled analysis, a significant OS benefit was found for nCRT in ESCC (HR=0.81, 95 %CI:0.67-0.98, p=0.029), compared with the treatment of nCT. The median overall survival time were 53 months (95 %CI:41.9-67.7 m) and 66 months(95 %CI:57.2-NA) respectively in the nCT and nCRT groups. Additionally, a significant improvement in PFS for nCRT compared to nCT in the IPD pooled analysis (HR=0.79,95 %CI:0.64-0.98; p=0.027). Consistent with above results, the pooled HRs of OS and DFS for nCRT versus nCT were 0.78 (95 % CI 0.65-0.92, p=0.004) and 0.79 (95 % CI: 0.65-0.97, p=0.02), respectively. Notably, no substantial heterogeneity across studies was observed. CONCLUSIONS: Our findings indicate that nCRT offers better survival outcomes for ESCC, at least when compared to neoadjuvant doublet chemotherapy.This evidence continues to support the clinical practice of employing nCRT in locally advanced resectable ESCC.

Association of ambient temperature and diurnal temperature range with the outcome of in vitro fertilization in women from Hubei, China: A retrospective cohort study.

OBJECTIVES: To examine the relationship between ambient temperature and DTR and pregnancy outcomes in vitro fertilization/intracytoplasmic monosperm injection and embryo transfer (IVF/ICSI-ET) women. METHODS: The study included 5,264 women who were treated with IVF/ICSI-ET at two centers in Hubei province from 2017 to 2022. The daily mean, daily maximum, and daily minimum temperatures at the subjects' home addresses were extracted, and DTR values were calculated based on latter two. The associations between ambient temperature and DTR with clinical pregnancy and live birth rates were assessed using multivariate logistic regression models adjusted for covariates. Subgroup analyses were also conducted to explore potential modifiers. RESULT: High/low temperatures as well as a larger DTR had a significant effect on pregnancy outcomes in fresh cycles, but not in FET cycles. Specifically, hot weather exposure to high temperatures was associated with reduced clinical pregnancy rates: Period4 (embryo transfer to serum HCG testing) (aOR = 0.873, 95%CI: 0.763-0.999). Ambient temperature in cold weather was positively associated with live birth rate: Period 2 (Gn initiation to oocyte retrieval) (aOR = 1.082, 95% CI: 1.01-1.170), Period 3 (oocyte retrieval to embryo transfer) (aOR = 1.111, 95% CI: 1.019-1.212), Period 4 (aOR = 1.134, 95% CI: 1.028-1.252), and Period7 (85 days prior to oocyte retrieval to serum hCG testing) (aOR = 1.105, 95% CI: 1.007-1.212). For DTR, exposure to larger DTR (Q3) at Period2, Period3, and Period6 (Gn initiation to embryo transfer) reduces clinical pregnancy and live birth rates compared with Q1. Subgroup analyses revealed susceptibility profiles across age groups and residential address populations in different sensitivity windows. CONCLUSION: Our study shows that exposure to hot and cold weather and higher DTR reduces clinical pregnancy rates and live birth rates in women undergoing fresh embryo transfer, but has no significant effect on FET cycles.

Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire.

The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response.

Resource Use and Care Quality Differences Among Medicare Beneficiaries Undergoing Chemotherapy.

Importance: Medicare Advantage (MA) has grown significantly over the last decade; however, MA's performance for patients with serious conditions, such as cancer, remains unclear. Objective: To compare resource use and care quality between MA and traditional Medicare (TM) beneficiaries undergoing cancer chemotherapy. Design, Setting, and Participants: This cohort study used TM claims and MA encounter records from January 2015 to December 2019. Participants were MA and TM beneficiaries who initiated cancer chemotherapy between January 2016 and December 2019. Inverse probability of treatment weighting balanced characteristics between MA and TM beneficiaries, and regression estimation was used. The analysis was conducted between August 2023 and May 2024. Exposure: Chemotherapy initiation after a 1-year washout period. Main Outcomes and Measures: Resource use and care quality were measured during a 6-month period following chemotherapy initiation. Resource use was measured using standardized prices for services in both MA and TM, covering hospital inpatient services, outpatient care, Part D drugs, and hospice services. Chemotherapy utilization was examined for Part B chemotherapy, Part B supportive drugs, and Part D chemotherapy. Quality measures included chemotherapy-related emergency department (ED) visits and hospitalizations, avoidable ED visits, preventable hospitalizations during the 6-month episode, and survival days up to 18 months from chemotherapy initiation. Results: The study comprised 96 501 MA enrollees contributing to 98 872 episodes (mean [SD] age, 72.9 [7.6] years; 55 859 [56.5%] female; 7371 [7.5%] Hispanic, 14 778 [14.9%] non-Hispanic Black, and 75 130 [75.0%] non-Hispanic White participants) and 206 274 TM beneficiaries, contributing 212 969 episodes (mean [SD] age, 72.7 [8.3] years; 121 263 [56.9%] female; 8356 [3.9%] Hispanic, 16 693 [7.8%] non-Hispanic Black, and 182 228 [85.6%] non-Hispanic White participants). Adjusted total resource use per enrollee during the 6-month episode was $8718 (95% CI, $8343 to $9094) lower in MA than TM ($62 599 vs $71 317). Part B chemotherapy resource use accounted for most of the difference in total resource use, with MA enrollees having $5032 (95% CI, $4772 to $5293) lower use than TM beneficiaries. Lower resource use for Part B chemotherapy in MA was associated with both fewer chemotherapy visits (-1.06 visits; 95% CI, -1.10 to -1.02 visits) and less expensive chemotherapy per visit (-$277; 95% CI, -$275 to -$179). Findings on quality were mixed, but importantly, survival did not differ between MA and TM patients who initiated chemotherapy. Conclusions and Relevance: In this cohort study of Medicare beneficiaries with cancer undergoing chemotherapy, MA enrollment was associated with lower resource use but not shorter survival.

Lung immune prognostic index is associated with clinical outcomes in recurrent or metastatic (R/M) nasopharyngeal carcinoma receiving immunotherapy: Results from the multicenter, single-arm, phase 2 study.

BACKGROUND: Immune-related biomarkers are linked to the outcomes of cancer immunotherapy. This study evaluates the baseline and longitudinal association between the lung immune prognostic index (LIPI) and immune checkpoint inhibitor outcomes in previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) patients. METHODS: Data from 153 R/M NPC patients (median age = 49.00 years old) enrolled in a multicenter, single-arm, phase 2 study (NCT03848286) were analyzed. Pretreatment LIPI was classified into good and intermediate/poor (inter/poor) groups. Longitudinal LIPI variations were categorized into "Stable good", "Trend to increase", "Trend to decrease", and "Stable inter/poor". Primary and secondary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). RESULTS: Pretreatment LIPI was significantly associated with OS (inter/poor vs. good: HR = 2.54, 95 % CI: 1.60-4.04, P < 0.001), PFS [inter/poor vs. good: hazard ratio (HR) = 2.18, 95 % CI: 1.47-3.23, P < 0.001], and DCR [inter/poor vs. good: odd ratio (OR) = 0.26, 95 % CI: 0.12-0.58, P < 0.001)]. Patients with persistently inter/poor LIPI status showed worse OS (HR = 3.25, 95 % CI: 1.84-5.74, P < 0.001), PFS (HR = 2.96, 95 % CI: 1.85-4.74, P < 0.001), and ORR (OR = 0.21, 95 % CI: 0.08-0.56, P < 0.001) compared to the persistently good subgroup. CONCLUSION: Pretreatment LIPI and its longitudinal variations may serve as potential biomarkers for predicting immune checkpoint inhibitor outcomes in R/M NPC patients.

Epitaxial Growth of Monolayer WS2 Single Crystals on Au(111) Toward Direct Surface-Enhanced Raman Spectroscopy Detection.

The epitaxial growth of wafer-scale two-dimensional (2D) semiconducting transition metal dichalcogenides (STMDCs) single crystals is the key premise for their applications in next-generation electronics. Despite significant advancements, some fundamental factors affecting the epitaxy growth have not been fully uncovered, e.g., interface coupling strength, adlayer-substrate lattice matching, substrate step-edge-guiding effects, etc. Herein, we develop a model system to tackle these issues concurrently, and realize the epitaxial growth of wafer-scale monolayer tungsten disulfide (WS2) single crystals on the Au(111) substrate. This epitaxial system is featured with good adlayer-substrate lattice matching, obvious step-edge-guiding effect for the unidirectionally aligned nucleation/growth, and relatively weaker interfacial interaction than that of monolayer MoS2/Au(111), as evidenced by the evolution of a uniform Moiré pattern and an intrinsic band gap, according to on-site scanning tunneling microscopy/spectroscopy (STM/STS) characterizations and density functional theory calculations. Intriguingly, the unidirectionally aligned monolayer WS2 domains along the Au(111) steps can behave as ultrasensitive templates for surface-enhanced Raman scattering detection of organic molecules, due to the obvious charge transfer occurred at substrate step edges. This work should hereby deepen our understanding of the epitaxy mechanism of 2D STMDCs on single-crystal substrates, and propel their wafer-scale production and applications in various cutting-edge fields.

Chinese expert consensus on management of antifungal-resistant dermatophytoses (2024 edition).

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.

Analysis of mortality in Parkinson disease in China: Exploration of recent and future trends.

Objectives: Parkinson disease (PD) is the third leading cause of mortality among middle-aged and older individuals in China. This study aimed to explore the trends and distribution features of PD mortality in China from 2013 to 2021 and make predictions for the next few decades. Methods: Relevant data were obtained from the Chinese Center for Disease Control and Prevention Disease Surveillance Point system. The joinpoint regression model was used to evaluate trends. The R software was used to predict future trends. Results: Age-standardized mortality rate (ASMR) of PD increased from 0.59 per 100,000 individuals to 1.22 per 100,000 individuals from 2013 to 2021, with an average annual percent change (AAPC) of 9.50 (95% CI: 8.24-10.78). The all-age ASMR of PD were higher in male individuals than in female individuals, and ASMR increased with age. The number of deaths and ASMR increased gradually from west to east and from rural to urban areas. Furthermore, ASMR is expected to increase to 2.66 per 100,000 individuals by 2040. Conclusions: The heightened focus on the ASMR of PD among male individuals, urban areas, eastern China, and individuals aged ≥85 years has become a key determinant in further decreasing mortality, thereby exhibiting novel challenges to effective strategies for disease prevention and control.

Performance enhancement and mechanism of electroenhanced peroxymonosulfate activation by single-atom Fe catalyst modified electrodes.

Peroxymonosulfate-based electrochemical advanced oxidation processes (PMS-EAOPs) have great potential for sustainable water purification, so an in-depth understanding of its catalytic mechanism is imperative to facilitate its practical application. Herein, the performance enhancement and mechanism of electroenhanced PMS activation by single-atom Fe catalyst modified carbon felt was investigated. Compared with the anode, the cathode exhibited faster bisphenol A degradation (kcathode = 0.073 vs. kanode = 0.015 min-1), increased PMS consumption (98.8 vs. 10.3%), and an order of magnitude reduction of Fe dissolution (0.068 vs. 0.787 mg L-1). Mass transfer is a key factor limiting PMS activation, while the electrostriction of water in the hydrophobic region caused by cathode electric field (CEF) significantly increased mass transfer coefficient (km, cathode = 1.49 × 10-4 vs. km, anode = 2.68 × 10-5 m s-1). The enhanced activation of PMS is a synergistic result between electroactivation and catalyst-activation, which is controlled by the applied current density. 1O2 and direct electron transfer are the main active species and activation pathway, which achieve high degradation efficiency over pH 3 to 10. Density functional theory calculations prove CEF increases the adsorption energy, lengthens the O-O bond in PMS, and promotes charge transfer. A flow-through convection unit achieves sustainable operation with high removal efficiency (99.5% to 97.5%), low electrical energy consumption (0.15 kWh log-1 m-3), and low Fe leaching (0.81% of the total single atom Fe). This work reveals the critical role of electric fields in modulating Fenton-like catalytic activity, which may advance the development of advanced oxidation processes and other electrocatalytic applications.

Subdivision of M1 category and prognostic stage for de novo metastatic breast cancer to enhance prognostic prediction and guide the selection of locoregional therapy.

BACKGROUND: Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment. METHODS: We selected patients with dnMBC from the SEER database (2010-2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010-2023) treated in three hospitals. Nomogram-based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses. RESULTS: Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram-based stratification effectively divided M1 stage into three groups: M1a (bone-only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage. CONCLUSION: Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment.

Effect of Terminal Phosphate Groups on Collisional Dissociation of RNA Oligonucleotide Anions.

The increasing need for mass spectrometric analysis of RNA molecules calls for a better understanding of their gas-phase fragmentation behaviors. In this study, we investigate the effect of terminal phosphate groups on the fragmentation spectra of RNA oligonucleotides (oligos) using high-resolution mass spectrometry (MS). Negative-ion mode collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD) were carried out on RNA oligos containing a terminal phosphate group on either end, both ends, or neither end. We find that terminal phosphate groups affect the fragmentation behavior of RNA oligos in a way that is dependent on the precursor charge state and the oligo length. Specifically, for precursor ions of RNA oligos of the same sequence, those with 5'- or 3'-phosphate, or both, have a higher charge state distribution and lose the phosphate group(s) in the form of a neutral (H3PO4 or HPO3) or an anion ([H2PO4]- or [PO3]-) upon CID or HCD. Such a neutral or charged loss is most conspicuous for precursor ions of an intermediate charge state, e.g., 3- for 4-nt oligos or 4- and 5- for 8-nt oligos. This decreases the intensity of sequencing ions (a-, a-B, b-, c-, d-, w-, x-, y-, z-ions) and hence is unfavorable for sequencing by CID or HCD. Removal of terminal phosphate groups by calf intestinal alkaline phosphatase improved MS analysis of RNA oligos. Additionally, the intensity of a fragment ion at m/z 158.925, which we identified as a dehydrated pyrophosphate anion ([HP2O6]-), is markedly increased by the presence of a terminal phosphate group. These findings expand the knowledge base necessary for software development for MS analysis of RNA.

Associations between Patient-Generated Subjective Global Assessment criteria and all-cause mortality among cancer patients: Evidence from baseline and longitudinal analyses.

OBJECTIVES: The prognostic effects of the Patient-Generated Subjective Global Assessment (PG-SGA) criteria in cancer survivors have been observed but require validation in clinical practice. This study was designed to evaluate the prognostic effects of baseline and longitudinal changes in PG-SGA scores on all-cause mortality among Chinese cancer patients in a real-world setting. METHODS: Study patients were selected from one representative tertiary hospital in West China. Kaplan-Meier curves and Cox regression analyses were used to estimate the prognostic effect of baseline and dynamic changes in PG-SGA scores on the all-cause mortality of cancer patients. Receiver operating characteristic curves and a concordance index were used to evaluate the predictive accuracy of PG-SGA criteria. RESULTS: A total of 1415 cancer patients were included in this study, with a mean age of 46 years old. Cox regression analysis showed that baseline malnourished status was significantly associated with the survival of cancer patients (PG-SGA 4-8: hazard ratio [HR] = 1.46, 95% confidence interval [CI]: 1.09-1.96, P = 0.012; PG-SGA ≥9: HR = 1.78, 95% CI: 1.34-2.37, P < 0.001). Cancer patients with longitudinal increased PG-SGA scores (>2 points) were observed to have high risks for mortality (HR = 1.69, 95% CI: 1.04-2.74, P = 0.033). Compared with longitudinal changes in PG-SGA scores, baseline malnourished status showed higher predictive power in identifying the risk subgroup (concordance index: 0.646 vs. 0.586). Sensitivity analyses supported the main findings. CONCLUSIONS: This study highlights the prognostic value of baseline and dynamic changes in PG-SGA scores for cancer patients, which can help improve their outcomes.

Highly efficient FeS/Fe3O4 @ biomass carbon bifunctional catalyst with enriched oxygen vacancies for heterogeneous electro-Fenton catalysis.

Low H2O2 production, narrow adaptive pH range and slow Fe(II) regeneration on the cathode still limit efficiency of electro-Fenton (EF) and its application. Herein, we designed a bifunctional catalyst with FeS and Fe3O4 nanoparticles dispersed on porous carbon (CFeS@C) using template of sodium alginate (SA)/FeSO4 hydrogel mixed with carbon black (CB), which presented high H2O2 generation efficiency and outstanding tetracycline degradation efficiency under wide pH ranges (3-8) with a low energy consumption of 19.6 kWh/kg total organic carbon (TOC). The introduction of CB created abundant oxygen vacancies in CFeS@C, promoting the oxygen adsorption and the electrochemical generation of H2O2, which further boosted the formation of •OH due to the interaction with Fe2+ on the cathode surface. Simultaneously, the reaction between the outer layer of FeS and Fe3+ not only accelerated iron cycling but also reduced the solution pH. It was verified that •OH and 1O2 played a dominant role in organics degradation. The system maintained stability after 10 cycles and effectiveness in the treatment of pharmaceutical wastewater. This study would offer a new strategy to develop an efficient and durable bifunctional catalyst for heterogeneous EF system working in wide pH conditions for wastewater treatment.

Nanoparticle-Based Therapies for Neurotropic Viral Infections: Mechanisms, Challenges, and Future Prospects.

Neurotropic viral infections pose a significant challenge due to their ability to target the central nervous system and cause severe neurological complications. Traditional antiviral therapies face limitations in effectively treating these infections, primarily due to the blood-brain barrier, which restricts the delivery of therapeutic agents to the central nervous system. Nanoparticle-based therapies have emerged as a promising approach to overcome these challenges. Nanoparticles offer unique properties that facilitate drug delivery across biological barriers, such as the blood-brain barrier, and can be engineered to possess antiviral activities.

Synergy of atomic hydrogen reduction and reactive oxygen species oxidation over confined Mn bifunctional site for electrocatalytic deep mineralization.

Traditional reduction or oxidation processes generating one-component free radicals face challenges in deep dechlorination and mineralization of chlorophenols from wastewater. Herein, an efficient electrocatalytic process has been developed, which couples atomic H* reduction with reactive oxidation species (•OH and 1O2) oxidation on a bifunctional cathode for 4 -chlorophenol (4 -CP) removal. The N - doped carbon nanotubes encapsulated manganese nanoparticles was fabricated as cathode, which could generate atomic H* , initiating nucleophilic hydrodechlorination in presence of confined MnO sites. Subsequently, electrophilic oxidation by generating mainly 1O2 on confined Mn7C3 sites and •OH on confined MnO sites, facilitating the oxidative processes. Experimental results and theory calculations demonstrated that reductive dechlorination and oxidative mineralization processes could mutually promote each other, resulting in an enhancement factor of 2.90. At pH 7, this process achieved 100 % removal for 4 -CP, 84 % dechlorination, 76 % total organic carbon (TOC) removal and low energy consumption (0.76 kWh g-1TOC) within 120 min. Notably, TOC for chlorophenols containing Cl substituents at different positions and real lake water containing 4 -CP could be almost completely removed. This research establishes confined non-noble bifunctional active sites that synergistically enhance reductive dechlorination and oxidative degradation processes, holding significant treatment potential for application in deep mineralization of organochlorine from water/wastewater.

Ultrasonication as anaerobic digestion pretreatment to improve sewage sludge methane production: Performance and microbial characterization.

A large amount of sludge is inevitably produced during sewage treatment. Ultrasonication (US) as anaerobic digestion (AD) pretreatment was implemented on different sludges and its effects on batch and semi-continuous AD performance were investigated. US was effective in sludge SCOD increase, size decrease, and CH4 production in the subsequent AD, and these effects were enhanced with an elevated specific energy input. As indicated by semi-continuous AD experiments, the mean daily CH4 production of US-pretreated A2O-, A2O-MBR-, and AO-AO-sludge were 176.9, 119.8, and 141.7 NmL/g-VSadded, which were 35.1%, 32.1% and 78.2% higher than methane production of their respective raw sludge. The US of A2O-sludge achieved preferable US effects and CH4 production due to its high organic content and weak sludge structure stability. In response to US-pretreated sludge, a more diverse microbial community was observed in AD. The US-AD system showed negative net energy; however, it exhibited other positive effects, e.g., lower required sludge retention time and less residual total solids for disposal. US is a feasible option prior to AD to improve anaerobic bioconversion and CH4 yield although further studies are necessary to advance it in practice.

Excited-Ground-State Transition of the RNA Strand Slippage Mechanism Captured by the Base-Specific Force Field.

Excited-ground-state transition and strand slippage of RNA play key roles in transcription and translation of central dogma. Due to limitation of current experimental techniques, the dynamic structure ensembles of RNA remain inadequately understood. Molecular dynamics simulations offer a promising complementary approach, whose accuracy depends on the force field. Here, we develop the new version of RNA base-specific force field (BSFF2) to address underestimation of base pairing stability and artificial backbone conformations. Extensive evaluations on typical RNA systems have comprehensively confirmed the accuracy of BSFF2. Furthermore, BSFF2 demonstrates exceptional efficiency in de novo folding of tetraloops and reproducing base pair reshuffling transition between RNA excited and ground states. Then, we explored the RNA strand slippage mechanism with BSFF2. We conducted a comprehensive three-dimensional structural investigation into the strand slippage of the most complex r(G4C2)9 repeat element and presented the molecular details in the dynamic transition along with the underlying mechanism. Our results of capturing the strand slippage, excited-ground transition, de novo folding, and simulations for various typical RNA motifs indicate that BSFF2 should be one of valuable tools for dynamic conformation research and structure prediction of RNA, and a future contribution to RNA-targeted drug design as well as RNA therapy development.

Longitudinal Associations among Psychological Control, Positive and Negative Interactions, and Adolescents' Domain-Specific Disclosure to Parents.

Although much research has shown that parental psychological control undermines adolescents' routine disclosure to parents, past research has not examined whether the effects of psychological control on disclosure are domain-specific and mediated by the quality of adolescents' interactions with mothers and fathers. The present one-year longitudinal study examined whether parental support and negative interactions with each parent mediated longitudinal associations between adolescents' ratings of psychological control and adolescents' disclosure about routine prudential, personal, and multifaceted activities, as defined by social domain theory. These issues were examined over one year in 174 mostly White (74%), U.S. middle class middle adolescents (M = 15.70 years, SD = 0.63, 83 males). Greater parental psychological control was associated over time with less disclosure to both parents about personal activities and less disclosure to fathers about multifaceted issues. Perceived declines in support fully mediated the effects of psychological control on adolescent disclosure to mothers about personal issues and partially mediated the effects on disclosure to fathers about personal and multifaceted issues. In addition, negative interactions led to decreased disclosure about prudential issues. Thus, perceived psychological control and relationship quality had domain-specific and parent-specific longitudinal effects on adolescent disclosure to parents about their routine activities.

OIP5-AS1 enhances the malignant characteristics and resistance to chemotherapy of pancreatic cancer cells by targeting miR-30d-5p/MARCH8.

MARCH8, an E3 ubiquitin ligase, plays a crucial role in regulating various cellular processes such as protein degradation and signaling pathways and is implicated in the development and spread of pancreatic cancer. Analysis of pancreatic cancer tissues compared to adjacent normal tissues showed a decrease in miRNA-30d-5p levels and an increase in OIP5-AS1 and MARCH8 levels, as confirmed by qRT-PCR and Western blot analysis. The dual-luciferase reporter assay demonstrated a binding relationship between OIP5-AS1 and miRNA-30d-5p, as well as between miRNA-30d-5p and MARCH8 in PACN-1 cells, derived from a human pancreatic carcinoma specimen. Further investigations utilizing various assays revealed that OIP5-AS1 inhibited apoptosis and promoted cell proliferation, invasion, and migration in PACN-1 cells via the miRNA-30d-5p/MARCH8 axis in vitro. Tumor experiments in nude mice confirmed that OIP5-AS1 enhanced PACN-1 cell growth in vivo through the miRNA-30d-5p/MARCH8 axis. Additionally, OIP5-AS1 was found to activate downstream genes of the JAK-STAT pathway, namely IFNAR2, SOCS3, and JAK1, in PACN-1 cells. Furthermore, OIP5-AS1 increased the IC50 values for doxorubicin, gemcitabine, and cisplatin in PACN-1 cells, as determined by the Cell Counting Kit-8 assay. Overall, OIP5-AS1 was shown to promote aggressive traits and resistance to chemotherapy in PACN-1 cells through the miRNA-30d-5p/MARCH8 axis.

Foliar-selenium enhances plant growth and arsenic accumulation in As-hyperaccumulator Pteris vittata: Critical roles of GSH-GSSG cycle and arsenite antiporters PvACR3.

It is known that selenium (Se) enhances plant growth and arsenic (As) accumulation in As-hyperaccumulator Pteris vittata, but the associated mechanisms are unclear. In this study, P. vittata was exposed to 50 µM arsenate (AsV) under hydroponics plus 25 or 50 µM foliar selenate. After 3-weeks of growth, the plant biomass, As and Se contents, As speciation, malondialdehyde (MDA) and glutathione (GSH and GSSG) levels, and important genes related to As-metabolism in P. vittata were determined. Foliar-Se increased plant biomass by 17 - 30 %, possibly due to 9.1 - 19 % reduction in MDA content compared to the As control. Further, foliar-Se enhanced the As contents by 1.9-3.5 folds and increased arsenite (AsIII) contents by 64 - 136 % in the fronds. The increased AsV reduction to AsIII was attributed to 60 - 131 % increase in glutathione peroxidase activity, which mediates GSH oxidation to GSSG (8.8 -29 % increase) in the fronds. Further, foliar-Se increased the expression of AsIII antiporters PvACR3;1-3;3 by 1.6 - 2.1 folds but had no impact on phosphate transporters PvPht1 or arsenate reductases PvHAC1/2. Our results indicate that foliar-Se effectively enhances plant growth and arsenic accumulation by promoting the GSH-GSSG cycle and upregulating gene expression of AsIII antiporters, which are responsible for AsIII translocation from the roots to fronds and AsIII sequestration into the fronds. The data indicate that foliar-Se can effectively improve phytoremediation efficiency of P. vittata in As-contaminated soils.