H2 supplied via ammonia borane stimulates lateral root branching via phytomelatonin signaling.

A reliable and stable hydrogen gas (H2) supply will benefit agricultural laboratory and field trials. Here, we assessed ammonia borane (AB), an efficient hydrogen storage material used in the energy industry, and determined its effect on plant physiology and the corresponding mechanism. Through hydroponics and pot experiments, we discovered that AB increases tomato (Solanum lycopersicum) lateral root (LR) branching and this function depended on the increased endogenous H2 level caused by the sustainable H2 supply. In particular, AB might trigger LR primordia initiation. Transgenic tomato and Arabidopsis (Arabidopsis thaliana) expressing hydrogenase1 (CrHYD1) from Chlamydomonas reinhardtii not only accumulated higher endogenous H2 and phytomelatonin levels but also displayed pronounced LR branching. These endogenous H2 responses achieved by AB or genetic manipulation were sensitive to the pharmacological removal of phytomelatonin, indicating the downstream role of phytomelatonin in endogenous H2 control of LR formation. Consistently, extra H2 supply failed to influence the LR defective phenotypes in phytomelatonin synthetic mutants. Molecular evidence showed that the phytomelatonin-regulated auxin signaling network and cell-cycle regulation were associated with the AB/H2 control of LR branching. Also, AB and melatonin had little effect on LR branching in the presence of auxin synthetic inhibitors. Collectively, our integrated approaches show that supplying H2 via AB increases LR branching via phytomelatonin signaling. This finding might open the way for applying hydrogen storage materials to horticultural production.

Molecular hydrogen positively regulates nitrate uptake and seed size by targeting nitrate reductase.

Although the sources of molecular hydrogen (H2) synthesis in plants remain to be fully elucidated, ample evidence shows that plant-based H2 can regulate development and stress responses. Here, we present genetic and molecular evidence indicating that nitrate reductase (NR) might be a target of H2 sensing that positively regulates nitrogen use efficiency (NUE) and seed size in Arabidopsis (Arabidopsis thaliana). The expression level of NR and changes of NUE under control and, in particular, low nitrogen supply were positively associated with H2 addition supplied exogenously or through genetic manipulation. The improvement in nitrate assimilation achieved by H2 was also mediated via NR dephosphorylation. H2 control of seed size was impaired by NR mutation. Further genetic evidence revealed that H2, NR, and nitric oxide can synergistically regulate nitrate assimilation in response to N starvation conditions. Collectively, our data indicate that NR might be a target for H2 sensing, ultimately positively regulating nitrate uptake and seed size. These results provide insights into H2 signaling and its functions in plant metabolism.

Physiologic oxygen responses to smoking opioids: an observational study using continuous pulse oximetry at overdose prevention services in British Columbia, Canada.

BACKGROUND: In British Columbia, Canada, smoking is the most common modality of drug use among people who die of opioid toxicity. We aimed to assess oxygen saturation (SpO2) while people smoked opioids during a pilot study that introduced continuous pulse oximetry at overdose prevention services (OPS) sites. METHODS: This was an observational cohort study, using a participatory design. We implemented our monitoring protocol from March to August 2021 at four OPS. We included adults (≥ 18 years) presenting to smoke opioids. A sensor taped to participants' fingers transmitted real-time SpO2 readings to a remote monitor viewed by OPS staff. Peer researchers collected baseline data and observed the timing of participants' inhalations. We analyzed SpO2 on a per-event basis. In mixed-effects logistic regression models, drop in minimum SpO2 ≤ 90% in the current minute was our main outcome variable. Inhalation in that same minute was our main predictor. We also examined inhalation in the previous minute, cumulative inhalations, inhalation rate, demographics, co-morbidities, and substance use variables. RESULTS: We recorded 599 smoking events; 72.8% (436/599) had analyzable SpO2 data. Participants' mean age was 38.6 years (SD 11.3 years) and 73.1% were male. SpO2 was highly variable within and between individuals. Drop in SpO2 ≤ 90% was not significantly associated with inhalation in that same minute (OR: 1.2 [0.8-1.78], p = 0.261) or inhalation rate (OR 0.47 [0.20-1.10], p = 0.082). There was an association of SpO2 drop with six cumulative inhalations (OR 3.38 [1.04-11.03], p = 0.043); this was not maintained ≥ 7 inhalations. Demographics, co-morbidities, and drug use variables were non-contributory. CONCLUSIONS: Continuous pulse oximetry SpO2 monitoring is a safe adjunct to monitoring people who smoke opioids at OPS. Our data reflect challenges of real-world monitoring, indicating that greater supports are needed for frontline responders at OPS. Inconsistent association between inhalations and SpO2 suggests that complex factors (e.g., inhalation depth/duration, opioid tolerance, drug use setting) contribute to hypoxemia and overdose risk while people smoke opioids.

Feeling safer: effectiveness, feasibility, and acceptability of continuous pulse oximetry for people who smoke opioids at overdose prevention services in British Columbia, Canada.

BACKGROUND: Smoking is the most common mode of unregulated opioid consumption overall and implicated in fatal overdoses in British Columbia (BC). In part, perception of decreased risk (e.g., fewer who smoke carry naloxone kits) and limited smoking-specific harm reduction services contribute to overdose deaths. Overdose prevention services (OPS) offer supervised settings for drug use. Continuous pulse oximetry, common in acute care, allows real-time, remote oxygen monitoring. We evaluated the effectiveness of a novel continuous pulse oximetry protocol aimed at allowing physical distancing (as required by COVID-19, secluded spaces, and to avoid staff exposure to vaporized opioids), its feasibility, and acceptability at OPS for people who smoke opioids. METHODS: This was a mixed methods survey study. We developed a continuous pulse oximetry protocol in collaboration with clinical experts and people with lived/living experience of substance use. We implemented our protocol from March to August 2021 at four OPS in BC permitting smoking. We included adults (≥ 18 years) presenting to OPS to smoke opioids. Peer researchers collected demographic, health, and substance use information, and conducted structured observations. OPS clients participating in our study, OPS staff, and peer researchers completed post-monitoring surveys. We analyzed responses using a thematic inductive approach and validated themes with peer researchers. RESULTS: We included 599 smoking events. OPS clients participating in our study had a mean age of 38.5 years; 73% were male. Most (98%) reported using "down", heroin, or fentanyl; 48% concurrently used other substances (32% of whom reported stimulants); 76% reported smoking alone in the last 3 days; and 36% reported an overdose while smoking. Respondents reported that the protocol facilitated physical distancing, was easy to use, high satisfaction, improved confidence, improved sense of safety, and that they would use it again. CONCLUSIONS: Continuous pulse oximetry allowed safe physical distancing, was feasible, and acceptable in monitoring people who smoke opioids at OPS.

A methane-cGMP module positively influences adventitious rooting.

KEY MESSAGE: Endogenous cGMP operates downstream of CH4 control of adventitious rooting, following by the regulation in the expression of cell cycle regulatory and auxin signaling-related genes. Methane (CH4) is a natural product from plants and microorganisms. Although exogenously applied CH4 and cyclic guanosine monophosphate (cGMP) are separately confirmed to be involved in the control of adventitious root (AR) formation, the possible interaction still remains elusive. Here, we observed that exogenous CH4 not only rapidly promoted cGMP synthesis through increasing the activity of guanosine cyclase (GC), but also induced cucumber AR development. These responses were obviously impaired by the removal of endogenous cGMP with two GC inhibitors. Anatomical evidence showed that the emerged stage (V) among AR primordia development might be the main target of CH4-cGMP module. Genetic evidence revealed that the transgenic Arabidopsis that overexpressed the methyl-coenzyme M reductase gene (MtMCR) from Methanobacterium thermoautotrophicum not only increased-cGMP production, but also resulted in a pronounced AR development compared to wild-type (WT), especially with the addition of CH4 or the cell-permeable cGMP derivative 8-Br-cGMP. qPCR analysis confirmed that some marker genes associated with cell cycle regulatory and auxin signaling were closely related to the brand-new CH4-cGMP module in AR development. Overall, our results clearly revealed an important function of cGMP in CH4 governing AR formation by modulating auxin-dependent pathway and cell cycle regulation.

Phytomelatonin and gasotransmitters: a crucial combination for plant physiological functions.

Melatonin, a molecule that was first identified in animal tissues, has been confirmed to be involved as a potential phytohormone in a variety of plant physiological responses. It is considered primarily as an antioxidant with important actions in controlling reactive oxygen and reactive nitrogen species. In addition to its role in regulating plant growth and development, phytomelatonin is involved in protection against abiotic and biotic stresses. The 'gasotransmitter'-that is, a gaseous signaling molecule-is a new concept that has been advanced in the past two decades, with functions in animal and plant physiological regulation. Gasotransmitters including nitric oxide, carbon monoxide, hydrogen sulfide, methane, and, more recently identified, hydrogen gas are critical and indispensable in a wide range of biological processes. This review investigates the interrelationship between phytomelatonin and the above-mentioned gasotransmitters from the perspective of biosynthetic origin and functions. Moreover, the potential future research directions for phytomelatonin and gasotransmitters interactions are discussed.

Characterizing people with frequent emergency department visits and substance use: a retrospective cohort study of linked administrative data in Ontario, Alberta, and B.C., Canada.

BACKGROUND: Substance use is common among people who visit emergency departments (EDs) frequently. We aimed to characterize subgroups within this cohort to better understand care needs/gaps, and generalizability of characteristics in three Canadian provinces. METHODS: This was a retrospective cohort study (April 1st, 2013 to March 31st, 2016) of ED patients in Ontario, Alberta, and British Columbia (B.C.) We included patients ≥ 18 years with substance use-related healthcare contact during the study period and frequent ED visits, defined as those in the top 10% of ED utilization when all patients were ordered by annual ED visit number. We used linked administrative databases including ED visits and hospitalizations (all provinces); mental heath-related hospitalizations (Ontario and Alberta); and prescriptions, physician services, and mortality (B.C.). We compared to cohorts of people with (1) frequent ED visits and no substance use, and (2) non-frequent ED visits and substance use. We employed cluster analysis to identify subgroups with distinct visit patterns and clinical characteristics during index year, April 1st, 2014 to March 31st, 2015. RESULTS: In 2014/15, we identified 19,604, 7,706, and 9,404 people with frequent ED visits and substance use in Ontario, Alberta, and B.C (median 37-43 years; 60.9-63.0% male), whose ED visits and hospitalizations were higher than comparison groups. In all provinces, cluster analyses identified subgroups with "extreme" and "moderate" frequent visits (median 13-19 versus 4-6 visits/year). "Extreme" versus "moderate" subgroups had more hospitalizations, mental health-related ED visits, general practitioner visits but less continuity with one provider, more commonly left against medical advice, and had higher 365-day mortality in B.C. (9.3% versus 6.6%; versus 10.4% among people with frequent ED visits and no substance use, and 4.3% among people with non-frequent ED visits and substance use). The most common ED diagnosis was acute alcohol intoxication in all subgroups. CONCLUSIONS: Subgroups of people with "extreme" (13-19 visits/year) and "moderate" (4-6 visits/year) frequent ED visits and substance use had similar utilization patterns and characteristics in Ontario, Alberta, and B.C., and the "extreme" subgroup had high mortality. Our findings suggest a need for improved evidence-based substance use disorder management, and strengthened continuity with primary and mental healthcare.

Packaging with hydrogen gas modified atmosphere can extend chicken egg storage.

BACKGROUND: Although hydrogen gas (H2 ) has been widely used in industry and gradually used in medicine, it is less applied to agriculture, especially in modified atmosphere packing (MAP). RESULTS: During chicken egg storage, H2 MAP not only slowed down or delayed the reduction in antioxidant capacities, but also alleviated the deterioration of egg quality. The extent of micro-cracks in the eggshell was also negatively influenced by H2 , which might result in eggs being less vulnerable to microbes. The earlier results demonstrated that the H2 MAP-extended shelf life of chicken eggs might be caused by the responses of eggshell and re-establishment of redox homeostasis. According to the data collected from different provinces of China, cost-economics analysis further suggested that the increase in the extra cost caused by H2 was trivial compared with the original price of eggs. CONCLUSION: Together, H2 MAP can prolong the shelf life of chicken eggs with the prospect of wider application. © 2021 Society of Chemical Industry.

Long sleep duration predicts a higher risk of obesity in adults: a meta-analysis of prospective cohort studies.

BACKGROUND: The connections between long sleep duration and obesity or weight gain warrant further examination. This meta-analysis aimed to evaluate whether long sleep duration was associated with the risk of obesity, weight gain, body mass index (BMI) change or weight change in adults. METHODS: PubMed, Embase, Cochrane Library, Elsevier Science Direct, Science Online, MEDLINE and CINAHL were searched for English articles published before May 2017. A total of 16 cohort studies (n = 329 888 participants) from 8 countries were included in the analysis. Pooled relative risks (RR) or regression coefficients (ß) with 95% confidence intervals (CI) were estimated. Heterogeneity and publication bias were tested, and sensitivity analysis was also performed. RESULTS: We found that long sleep duration was associated with higher risk of obesity (RR [95% CI] = 1.04 [1.00-1.09], P = 0.037), but had no significant associations with weight gain, BMI change or weight change. Long sleep duration increased the risk of weight gain in three situations: among men, in studies with <5 years follow-up, and when sleep duration was 9 or more hours. CONCLUSIONS: Long sleep duration was associated with risk of obesity in adults. More cohort studies with objective measures are needed to confirm this relationship.

Transcriptional Factors Mediating Retinoic Acid Signals in the Control of Energy Metabolism.

Retinoic acid (RA), an active metabolite of vitamin A (VA), is important for many physiological processes including energy metabolism. This is mainly achieved through RA-regulated gene expression in metabolically active cells. RA regulates gene expression mainly through the activation of two subfamilies in the nuclear receptor superfamily, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RAR/RXR heterodimers or RXR/RXR homodimers bind to RA response element in the promoters of RA target genes and regulate their expressions upon ligand binding. The development of metabolic diseases such as obesity and type 2 diabetes is often associated with profound changes in the expressions of genes involved in glucose and lipid metabolism in metabolically active cells. RA regulates some of these gene expressions. Recently, in vivo and in vitro studies have demonstrated that status and metabolism of VA regulate macronutrient metabolism. Some studies have shown that, in addition to RARs and RXRs, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter-transcription factor II, and peroxisome proliferator activated receptor ß/δ may function as transcriptional factors mediating RA response. Herein, we summarize current progresses regarding the VA metabolism and the role of nuclear receptors in mediating RA signals, with an emphasis on their implication in energy metabolism.

Bio-inspired, sensitivity-enhanced, bi-directional airflow sensor for turbulence detection.

Detecting airflow turbulence precursors promptly is crucial for ensuring flight safety and control. The initial stages of turbulence involve small reverse flows with random velocities and directions, which are not easily detected by existing airflow sensors. In this study, we designed a bionic, sensitivity-enhanced, bi-directional airflow sensor (BSBA) by incorporating bio-inspired circular tip slits and enlarging the central part of the cruciform beam structure. The BSBA exhibits a rapid response time (24.1 ms), high sensitivity (1.36 mV m-1 s-1), consistent detection of forward and backward airflow (correlation coefficient of 0.9854), and a low airflow detection threshold (1 ml). With these features, the proposed sensor can rapidly and accurately measure slight variations in the oscillating airflow, flow field, and contact force. The BSBA also achieves transparent obstacle detection on a quadrotor, even in visually challenging environments, by capturing minute changes in the flow fields produced by the quadrotor when encountering obstacles. The sensor's high sensitivity, consistent bi-directional detection, and fast response give it significant potential for enhancing safety in aircraft control systems.

Using quality improvement approaches to increase emergency department provider engagement in research participant enrollment during COVID-19 and opioid overdose public health emergencies.

PURPOSE: We utilized quality improvement (QI) approaches to increase emergency department (ED) provider engagement with research participant enrollment during the opioid crisis and coronavirus disease (COVID-19) pandemic. The context of this work is the Evaluating Microdosing in the Emergency Department (EMED) study, a randomized trial offering buprenorphine/naloxone to ED patients through randomization to standard or microdosing induction. Engaging providers is crucial for participant recruitment to our study. Anticipating challenges sustaining long-term engagement after a 63% decline in provider referrals four months into enrollments, we applied Plan-Do-Study-Act (PDSA) cycles to develop and implement an engagement strategy to increase and sustain provider engagement by 50% from baseline within 9 months. METHODS: Our engagement strategy was centered on Coffee Carts rounds: 5-min study-related educational presentations for providers on shift; and a secondary initiative, a Suboxone Champions program, to engage interested providers as study-related peer educators. We used provider referrals to our team as a proxy for study engagement and report the percent change in mean weekly referrals across two PDSA cycles relative to our established referral baseline. RESULTS: A QI approach afforded real-time review of interventions based on research and provider priorities, increasing engagement via mean weekly provider referrals by 14.5% and 49% across two PDSA cycles relative to baseline, respectively. CONCLUSIONS: Our Coffee Carts and Suboxone Champions program are efficient, low-barrier, educational initiatives to convey study-related information to providers. This work supported our efforts to maximally engage providers, minimize burden, and provide life-saving buprenorphine/naloxone to patients at risk of fatal overdose.

RéSUMé: BUT: Nous avons utilisé des approches d'amélioration de la qualité (AQ) pour accroître l'engagement des fournisseurs des services d'urgence (SU) avec l'inscription des participants à la recherche pendant la crise des opioïdes et la pandémie de maladie à coronavirus (COVID-19). Le contexte de ce travail est l'étude Evaluating Microdosing in the Emergency Department (EMED), un essai randomisé offrant de la buprénorphine/naloxone aux patients aux urgences par randomisation à l'induction standard ou au microdosage. L'engagement des fournisseurs est crucial pour le recrutement des participants à notre étude. En anticipant les difficultés à maintenir un engagement à long terme après une baisse de 63 % des recommandations de fournisseurs quatre mois après les inscriptions, nous avons appliqué le Plan-Do-Study-Act (PDSA) cycles d'élaboration et de mise en œuvre d'une stratégie d'engagement visant à accroître et à maintenir l'engagement des fournisseurs de 50 % par rapport au niveau de référence dans les neuf mois. MéTHODES: Notre stratégie de mobilisation était axée sur les tournées de Coffee Carts : des présentations éducatives de cinq minutes sur l'étude pour les fournisseurs sur le quart de travail; et une initiative secondaire, un programme Suboxone Champions, pour mobiliser les fournisseurs intéressés en tant que pairs éducateurs liés à l'étude. Nous avons utilisé les recommandations des fournisseurs à notre équipe comme indicateur de la participation à l'étude et nous avons signalé le pourcentage de changement dans les recommandations hebdomadaires moyennes pour deux cycles PDSA par rapport à notre base de référence établie. RéSULTATS: Une approche d'AQ a permis d'examiner en temps réel les interventions en fonction des priorités de la recherche et des fournisseurs, ce qui a augmenté l'engagement par l'intermédiaire des recommandations hebdomadaires moyennes des fournisseurs de 14,5 % et de 49 % au cours de deux cycles de PDSA par rapport au niveau de référence, respectivement. CONCLUSION: Notre programme Coffee Carts and Suboxone Champions est une initiative éducative efficace et peu contraignante qui permet de transmettre aux fournisseurs des renseignements sur les études. Ce travail a appuyé nos efforts visant à mobiliser au maximum les fournisseurs, à réduire au minimum le fardeau et à fournir de la buprénorphine/naloxone vitale aux patients à risque de surdose mortelle.

Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents.

A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 µM for AChE and 0.82-11.45 µM for BChE). A Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced Aß aggregation inhibitory activity at 20 µM with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease.

Molecular Hydrogen Confers Resistance to Rice Stripe Virus.

Although molecular hydrogen (H2) has potential therapeutic effects in animals, whether or how this gas functions in plant disease resistance has not yet been elucidated. Here, after rice stripe virus (RSV) infection, H2 production was pronouncedly stimulated in Zhendao 88, a resistant rice variety, compared to that in a susceptible variety (Wuyujing No.3). External H2 supply remarkably reduced the disease symptoms and RSV coat protein (CP) levels, especially in Wuyujing No.3. The above responses were abolished by the pharmacological inhibition of H2 production. The transgenic Arabidopsis plants overexpressing a hydrogenase gene from Chlamydomonas reinhardtii also improved plant resistance. In the presence of H2, the transcription levels of salicylic acid (SA) synthetic genes were stimulated, and the activity of SA glucosyltransferases was suppressed, thus facilitating SA accumulation. Genetic evidence revealed that two SA synthetic mutants of Arabidopsis (sid2-2 and pad4) were more susceptible to RSV than the wild type (WT). The treatments with H2 failed to improve the resistance to RSV in two SA synthetic mutants. The above results indicated that H2 enhances rice resistance to RSV infection possibly through the SA-dependent pathway. This study might open a new window for applying the H2-based approach to improve plant disease resistance. IMPORTANCE Although molecular hydrogen has potential therapeutic effects in animals, whether or how this gas functions in plant disease resistance has not yet been elucidated. RSV was considered the most devastating plant virus in rice, since it could cause severe losses in field production. This disease was thus selected as a classical model to explore the interrelationship between molecular hydrogen and plant pathogen resistance. In this study, we discovered that both exogenous and endogenous H2 could enhance plant resistance against Rice stripe virus infection by regulating salicylic acid signaling. Compared with some frequently used agrochemicals, H2 is almost nontoxic. We hope that the findings presented here will serve as an opportunity for the scientific community to push hydrogen-based agriculture forward.

Molecular hydrogen positively influences lateral root formation by regulating hydrogen peroxide signaling.

Although a previous study discovered that exogenous molecular hydrogen (H2) supplied with hydrogen-rich water (HRW) can mediate lateral root (LR) development, whether or how endogenous H2 influences LR formation is still elusive. In this report, mimicking the induction responses in tomato seedlings achieved by HRW or exogenous hydrogen peroxide (H2O2; a positive control), transgenic Arabidopsis that overexpressed the hydrogenase1 gene (CrHYD1) from Chlamydomonas reinhardtii not only stimulated endogenous hydrogen peroxide (H2O2) production, but also markedly promoted LR formation. Above H2 and H2O2 responses were abolished by the removal of endogenous H2O2. Moreover, the changes in transcriptional patterns of representative cell cycle genes and auxin signaling-related genes during LR development in both tomato and transgenic Arabidopsis thaliana matched with above phenotypes. The alternations in the levels of GUS transcripts driven by the CYCB1 promoter and expression of PIN1 protein further indicated that H2O2 synthesis was tightly linked to LR formation achieved by endogenous H2, and cell cycle regulation and auxin-dependent pathway might be their targets. There results might provide a reference for molecular mechanism underlying the regulation of root morphogenesis by H2.

Regulation of chlorothalonil degradation by molecular hydrogen.

Pesticides can accumulate throughout the food chain to potentially endanger human health. Although molecular hydrogen (H2) is widely used in industry and medicine, its application in agriculture is just beginning. This study showed that H2 enhances the degradation of the fungicide chlorothalonil (CHT) in plants, but does not reduce its antifungal efficacy. Pharmacological evidence confirmed the contribution of H2-stimulated brassinosteroids (BRs) in the above responses. The genetic increased endogenous H2 with overexpression of hydrogenase 1 gene (CrHYD1) from Chlamydomonas reinhardtii in Arabidopsis not only increased BRs levels, but also eventually intensified the degradation of CHT. Expression of genes encoding some enzymes responsible for detoxification in tomato and Arabidopsis were also stimulated. Contrasting responses were observed after the pharmacological removal of endogenous BR. We further proved that H2 control of CHT degradation was relatively universal, with at least since its degradation in Chinese cabbage, cucumber, radish, alfalfa, rice, and rapeseed were differentially enhanced by H2. Collectively, above results clearly indicated that both exogenously and endogenously applied with H2 could stimulate degradation of CHT partially via BR-dependent detoxification. These results may open a new window for environmental-friendly hydrogen-based agriculture.

Degradation of Carbendazim by Molecular Hydrogen on Leaf Models.

Although molecular hydrogen can alleviate herbicide paraquat and Fusarium mycotoxins toxicity in plants and animals, whether or how molecular hydrogen influences pesticide residues in plants is not clear. Here, pot experiments in greenhouse revealed that degradation of carbendazim (a benzimidazole pesticide) in leaves could be positively stimulated by molecular hydrogen, either exogenously applied or with genetic manipulation. Pharmacological and genetic increased hydrogen gas could increase glutathione metabolism and thereafter carbendazim degradation, both of which were abolished by the removal of endogenous glutathione with its synthetic inhibitor, in both tomato and in transgenic Arabidopsis when overexpressing the hydrogenase 1 gene from Chlamydomonas reinhardtii. Importantly, the antifungal effect of carbendazim in tomato plants was not obviously altered regardless of molecular hydrogen addition. The contribution of glutathione-related detoxification mechanism achieved by molecular hydrogen was confirmed. Our results might not only illustrate a previously undescribed function of molecular hydrogen in plants, but also provide an environmental-friendly approach for the effective elimination or reduction of pesticides residues in crops when grown in pesticides-overused environmental conditions.

Achieving Ultrasensitivity and Long-Term Durability Simultaneously for Microcantilevers Inspired by a Scorpion's Circular Tip Slits.

Microcantilevers are one of the most essential sensitive elements for various mechanical sensors. Their sensing performance determines the index level of a series of sensors. To date, the long-standing trade-off between ultrasensitivity and long-term durability of microcantilevers still remains a challenge. In nature, scorpions can sense vibrations as low as 10 nm amplitude through their circular tip slits sensilla. Such slit sensilla embedded in the exoskeleton of walking legs endure the compressing and stretching of every movement without spontaneous fracture failures. Here, we focused on the structural design of the circular tip slits which concentrate stress effectively and disperse energy smoothly, with the result that the microcantilevers are ultrasensitive and durable simultaneously in a single element. We devised a reproducible circular tip slits cantilever with enhanced sensitivity and ultralow detection limits to monitor 7 nm amplitude vibrations. The sensor possessed excellent durability and remained highly consistent with the correlation coefficient of nearly 0.999 over 100 000 cycles. Furthermore, the circular tip slits cantilever could precisely sense diverse subtle mechanical signals and exhibited potential applications in monitoring respiratory patterns. The simple geometric design can be easily manufactured on various sensory materials for applications requiring ultrahigh sensitivity and long-time durability.

The efficacy of PD-1 inhibitors in the maintenance treatment of diffuse large B-cell lymphoma: A single-center retrospective analysis.

Purpose: To explore the impact of PD-1 maintenance therapy on the relapse-free survival (RFS) of patients with diffuse large B-cell lymphoma (DLBCL). Methods: We retrospectively analyzed patients with DLBCL admitted to our center between January 2018 and July 2019 who achieved complete remission (CR) after induction chemotherapy. Forty-five patients who received PD-1 inhibitor maintenance therapy were considered the treatment group. Forty-five patients who did not undergo maintenance treatment during the same period were selected as the control group. The base levels of the two groups of patients were similar. The 2-year RFS rate of the two groups was compared. The correlation between the adverse prognosis factors of the patients and the RFS rate was performed subgroup analysis. Results: The 2-year RFS rates of the treatment and control groups were 86.7% VS 75.6% (P = 0.178), respectively, until July 2021. A single factor analysis showed that patients with International Prognostic Index (IPI) score ≥ 3, non-GCB DLBCL receiving PD-1 inhibitor maintenance treatment, can improve their 2-year RFS (72.2% VS 30.8%, P = 0.022; 88.5% VS 62.5%, P = 0.032). For non-GCB patients, the 2-year RFS of the treatment group can reach 88.5%, while the 2-year RFS of the control group is 62.5%, which is statistically significant (P = 0.032). In all patients treated with PD-1 inhibitors, the adverse reactions were all grade I-II, and there were no grade III-IV adverse reactions. There were no clear adverse events in the follow-up patients in the control group. Conclusion: Maintenance treatment with PD-1 inhibitors can improve the 2-year RFS rate of patients with IPI score of ≥3 and non-GCB DLBCL. This prompts the potential advantage of PD-1 inhibitors in DLBCL maintenance treatment. However, longer follow-ups remain needed to obtain more definite data.

Bioinspired, Omnidirectional, and Hypersensitive Flexible Strain Sensors.

Sensors are widely used in various fields, among which flexible strain sensors that can sense minuscule mechanical signals and are easy to adapt to many irregular surfaces are attractive for structure health monitoring, early detection, and failure prevention in humans, machines, or buildings. In practical applications, subtle and abnormal vibrations generated from any direction are highly desired to detect and even orientate their directions initially to eliminate potential hazards. However, it is challenging for flexible strain sensors to achieve hypersensitivity and omnidirectionality simultaneously due to the restrictions of many materials with anisotropic mechanical/electrical properties and some micro/nanostructures they employed. Herein, it is revealed that the vision-degraded scorpion detects subtle vibrations spatially and omnidirectionally using a slit sensillum with fan-shaped grooves. A bioinspired flexible strain sensor consisting of curved microgrooves arranged around a central circle is devised, exhibiting an unprecedented gauge factor of over 18 000 and stability over 7000 cycles. It can sense and recognize vibrations of diverse input waveforms at different locations, bouncing behaviors of a free-falling bead, and human wrist pulses regardless of sensor installation angles. The geometric designs can be translated to other material systems for potential applications including human health monitoring and engineering failure detection.