Tissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy.

Neoadjuvant immune checkpoint blockade has shown promising clinical activity. Here, we characterized early kinetics in tumor-infiltrating and circulating immune cells in oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 in a clinical trial (NCT02919683). Tumor-infiltrating CD8 T cells that clonally expanded during immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs, which were already active prior to therapy, supporting the capacity for rapid response. Systematic target discovery revealed that treatment-expanded tumor T cell clones in responding patients recognized several self-antigens, including the cancer-specific antigen MAGEA1. Treatment also induced a systemic immune response characterized by expansion of activated T cells enriched for tumor-infiltrating T cell clonotypes, including both pre-existing and emergent clonotypes undetectable prior to therapy. The frequency of activated blood CD8 T cells, notably pre-treatment PD-1-positive KLRG1-negative T cells, was strongly associated with intra-tumoral pathological response. These results demonstrate how neoadjuvant checkpoint blockade induces local and systemic tumor immunity.

Two members of a Nodule-specific Cysteine-Rich (NCR) peptide gene cluster are required for differentiation of rhizobia in Medicago truncatula nodules.

Legumes have evolved a nitrogen-fixing symbiotic interaction with rhizobia, and this association helps them to cope with the limited nitrogen conditions in soil. The compatible interaction between the host plant and rhizobia leads to the formation of root nodules, wherein internalization and transition of rhizobia into their symbiotic form, termed bacteroids, occur. Rhizobia in the nodules of the Inverted Repeat-Lacking Clade legumes, including Medicago truncatula, undergo terminal differentiation, resulting in elongated and endoreduplicated bacteroids. This transition of endocytosed rhizobia is mediated by a large gene family of host-produced nodule-specific cysteine-rich (NCR) peptides in M. truncatula. Few NCRs have been recently found to be essential for complete differentiation and persistence of bacteroids. Here, we show that a M. truncatula symbiotic mutant FN9285, defective in the complete transition of rhizobia, is deficient in a cluster of NCR genes. More specifically, we show that the loss of the duplicated genes NCR086 and NCR314 in the A17 genotype, found in a single copy in Medicago littoralis R108, is responsible for the ineffective symbiotic phenotype of FN9285. The NCR086 and NCR314 gene pair encodes the same mature peptide but their transcriptional activity varies considerably. Nevertheless, both genes can restore the effective symbiosis in FN9285 indicating that their complementation ability does not depend on the strength of their expression activity. The identification of the NCR086/NCR314 peptide, essential for complete bacteroid differentiation, has extended the list of peptides, from a gene family of several hundred members, that are essential for effective nitrogen-fixing symbiosis in M. truncatula.

A Prediction Rule for the Dystonic Spread of Blepharospasm: A 4-Year Prospective Cohort Study.

OBJECTIVE: Blepharospasm (BSP), focal dystonia with the highest risk of spread, lacks clear understanding of early spreading risk factors and objective prognostic indicators. We aimed to identify these risk factors through clinical and electrophysiological assessments, and to establish a predictive model for dystonic spread in BSP. METHODS: We prospectively followed BSP patients for 4 years, collecting data on dystonic spread, and conducting electrophysiological evaluations. The blink reflex, masseter inhibitory reflex, and trigeminal somatosensory evoked potential were assessed. Univariable and multivariable Cox proportional hazard regression models were used to assess clinical characteristics associated with BSP dystonic spread. A predictive model was constructed using a nomogram, and performance of the model was evaluated using the area under the receiver operating characteristic curve. RESULTS: A total of 136 enrolled participants (mean age 56.34 years) completed a 4-year follow-up. Among them, 62 patients (45.6%) showed spread to other body regions. Multivariable Cox regression analysis showed that a high Hamilton Anxiety Scale score (hazard ratio 1.19, 95% confidence interval 1.13-1.25, p < 0.001), prolonged trigeminal somatosensory evoked potential mandibular branch P1-N2 peak interval (hazard ratio 1.11, 95% confidence interval 1.02-1.21, p = 0.017), and elevated trigeminal somatosensory evoked potential mandibular branch P1-N2 peak amplitude (hazard ratio 1.26, 95% confidence interval 1.12-1.41, p < 0.001) were independent risk factors for BSP dystonic spread within 4 years. Combining these factors, the predictive models demonstrated excellent discriminative ability, with the receiver operating characteristic curve score being 0.797, 0.790, 0.847, and 0.820 at 1, 2, 3 and 4 years after enrollment, respectively. INTERPRETATION: We established a predictive model with significant value for anticipating dystonic spread in BSP, offering crucial evidence. These findings contribute essential insights into the early clinical identification of the development and evolution of BSP diseases. ANN NEUROL 2024.

Adult acute leukemia patients with gram-negative bacteria bloodstream infection: Risk factors and outcomes of antibiotic-resistant bacteria.

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p < 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

Dissolved LiO2 or adsorbed LiO2? The reactive superoxide during discharging process in lithium-oxygen batteries.

Lithium-oxygen batteries are promising but have many challenges. Unlike lithium-ion batteries, they are usually discharge-charge cycled with capacity cutoff instead of potential cutoff, which brings controversy. Additionally, which superoxide intermediate, the dissolved or the adsorbed superoxide, is more reactive and leads to cell premature death and unsatisfactory discharge capacity? These questions puzzle researchers and impede the development of lithium-oxygen batteries. Herein, on one hand, we tried to decouple the influence of discharging potential and discharging current density on the discharge products and side reactions. We found that the electrode potential has more impact on the side reactions than the current density. The low potential leads to a high ratio of Li2CO3 to Li2O2 in the discharge product and hence more surface passivation. On the other hand, to identify the more reactive and aggressive species that cause surface passivation, a flow cell setup was applied to suppress the solution route and maximize the products from the surface route. Results show that more Li2CO3 was identified under a large flow rate and thus the intermediates in surface route appear to be more reactive than that in solution route.

Evidence and Practical Applications of Site Occupancy Theory (SOT) of Eu3+ in Scheelite Compounds.

The determination of the site occupancy of activators in phosphors is essential for precise synthesis, understanding the relationship between their luminescence properties and crystal structure, and tailoring their properties by modifying the host composition. Herein, one simple method was proposed to help determine the sites at which the doping of rare earth ions or transition metal ions occupies in the host lattice through site occupancy theory (SOT) for ions doped into the matrix lattice. SOT was established based on the fact that doping ions preferentially occupy the sites with the lowest bonding energy deviations. In order to provide detailed experimental evidence to prove the feasibility of SOT, several scheelite-type compounds were successfully synthesized using a high-temperature solid-phase method. When Eu3+ ions occupy a similar surrounding environment site, the photoluminescence spectra of the activators Eu3+ are similar. Therefore, by comparing the intensity ratio of photoluminescence spectra and the mechanism of all transitions of KEu(WO4)2, KY(WO4)2:Eu3+, Na5Eu(WO4)4, and Na5Y(WO4)4:Eu3+, it was proved that SOT can successfully confirm the site occupation when doped ions enter the matrix lattice. SOT was further applied to the sites occupied by Eu3+ ion-doped LiAl(MoO4)2 and LiLu(MoO4)2.

Clinical and diagnostic values of metagenomic next-generation sequencing for infection in hematology patients: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis focused on systematically assessing the clinical value of mNGS for infection in hematology patients. METHODS: We searched for studies that assessed the clinical value of mNGS for infection in hematology patients published in Embase, PubMed, Cochrane Library, Web of Science, and CNKI from inception to August 30, 2023. We compared the detection positive rate of pathogen for mNGS and conventional microbiological tests (CMTs). The diagnostic metrics, antibiotic adjustment rate and treatment effective rate were combined. RESULTS: Twenty-two studies with 2325 patients were included. The positive rate of mNGS was higher than that of CMT (blood: 71.64% vs. 24.82%, P < 0.001; BALF: 89.86% vs. 20.78%, P < 0.001; mixed specimens: 82.02% vs. 28.12%, P < 0.001). The pooled sensitivity and specificity were 87% (95%CI: 81-91%) and 59% (95%CI: 43-72%), respectively. The reference standard/neutropenia and research type/reference standard may be sources of heterogeneity in sensitivity and specificity, respectively. The pooled antibiotic adjustment rate according to mNGS was 49.6% (95% CI: 41.8-57.4%), and the pooled effective rate was 80.9% (95% CI: 62.4-99.3%). CONCLUSION: mNGS has high positive detection rates in hematology patients. mNGS can guide clinical antibiotic adjustments and improve prognosis, especially in China.

PD-1/PD-L1 blockade is a potent adjuvant in treatment of Staphylococcus aureus osteomyelitis in mice.

There is no effective therapy for implant-associated Staphylococcus aureus osteomyelitis, a devastating complication after orthopedic surgery. An immune-suppressive profile with up-regulated programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) was identified based on our transcriptional data (GEO: GSE166522) from a mouse model of S. aureus osteomyelitis. PD-1/PD-L1 expression was up-regulated mainly in F4/80+ macrophages surrounding the abscess in S. aureus-infected bone. Mechanistically, PD-1/PD-L1 activated mitophagy to suppress production of mitochondrial reactive oxygen species (ROS), suppressing the bactericidal function of macrophages. Using neutralizing antibodies for PD-L1 or PD-1, or knockout of PD-L1 adjuvant to gentamicin markedly reduced mitophagy in bone marrow F4/80+ cells, enhanced bacterial clearance in bone tissue and implants, and reduced bone destruction in mice. PD-1/PD-L1 expression was also increased in the bone marrow from individuals with S. aureus osteomyelitis. These findings uncover a so far unknown function of PD-1/PD-L1-mediated mitophagy in suppressing the bactericidal function of bone marrow macrophages.

Development and validation of outcome prediction model for reperfusion therapy in acute ischemic stroke using nomogram and machine learning.

OBJECTIVE: To develop logistic regression nomogram and machine learning (ML)-based models to predict 3-month unfavorable functional outcome for acute ischemic stroke (AIS) patients undergoing reperfusion therapy. METHODS: Patients undergoing reperfusion therapy (intravenous thrombolysis and/or endovascular treatment) were prospectively recruited. Unfavorable outcome was defined as 3-month modified Rankin Scale (mRS) score 3-6. The independent risk factors associated with unfavorable outcome were obtained by regression analysis and included in the prediction model. The performance of nomogram was assessed by the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). ML models were compared with nomogram using AUC; the generalizability of all models was ascertained in an external cohort. RESULTS: A total of 505 patients were enrolled, with 256 in the model construction, and 249 in the external validation. Five variables were identified as prognostic factors: baseline NIHSS, D-dimer level, random blood glucose (RBG), blood urea nitrogen (BUN), and systolic blood pressure (SBP) before reperfusion. The AUC values of nomogram were 0.865, 0.818, and 0.779 in the training set, test set, and external validation, respectively. The calibration curve and DCA indicated appreciable reliability and good net benefits. The best three ML models were extra trees (ET), CatBoost, and random forest (RF) models; all of them showed favorable discrimination in the training cohort, and confirmed in the test and external sets. CONCLUSION: Baseline NIHSS, D-dimer, RBG, BUN, and SBP before reperfusion were independent predictors for 3-month unfavorable outcome after reperfusion therapy in AIS patients. Both nomogram and ML models showed good discrimination and generalizability.

Psychological challenges and quality of life in Pakistani parents of children living with thalassemia.

PURPOSE: Children living with thalassemia experience psychological challenges, but despite significant psychosocial burdens, caregivers' psychological wellbeing and quality of life remain understudied, particularly in lower-and-middle-income countries. DESIGN AND METHOD: The current study evaluated these relationships in 100 male and female Pakistani caregivers (23-45 years; 61% female) using Ryff's Psychological Well-Being Scale and the Singapore Caregiver Quality of Life Scale. Caregivers completed questionnaires during regularly scheduled clinic visits for their child. RESULTS: We found that Pakistani caregivers in our sample generally had significantly lower (30-40 points) quality of life than a referent sample of caregivers of older adults (ps < 0.001). Self-acceptance and personal growth were consistently significant predictors across quality of life domains. Further, significant interactions were observed. Female caregivers with less self-acceptance had worse mental health and wellbeing and impact on daily life (p < .05). Male caregivers with less personal growth had worse physical health wellbeing (p < .05). CONCLUSIONS: Our results demonstrate the importance of considering how distinct aspects of psychological wellbeing, rather than just the overall score, relate to the specific quality of life domains among male and female caregivers. PRACTICE IMPLICATIONS: Pediatric nurses are at the frontline of service delivery for children and are in a prime position to observe caregivers who could be at high risk for psychological challenges. Given our findings, future clinical interventions should prioritize support services promoting personal growth and self-acceptance for Pakistani caregivers of children living with thalassemia.

Anterior peri-sacroiliac joint osteotomy in the treatment of malunion and nonunion of complex pelvic ring fracture: techniques and preliminary results.

PURPOSE: To introduce anterior peri-sacroiliac joint osteotomy (APSJO) through the lateral-rectus approach (LRA) for treating pelvic fracture malunion and nonunion, and to evaluate the safety, feasibility, and potential effectiveness. METHODS: Data of 15 patients with pelvic fracture malunion and nonunion who underwent treatment by APSJO were selected and analyzed. The reduction quality was assessed using the Mears and Velyvis criteria, while the pre-operative and post-operative function was revealed by the Majeed scoring system. The British Medical Research Council (BMRC) grading system was recruited for the evaluation of lumbosacral plexus function. RESULTS: The average operative duration was 264.00 ± 86.75 min, while the intra-operative blood loss was 2000 (600, 3000) mL. Anatomical reduction was complete in three cases, satisfactory in ten cases, and unsatisfactory in two cases. Among the seven patients with lumbosacral plexus injury, the pre-operative Majeed grades were good in two cases, fair in two cases, and poor in three cases, while the post-operative Majeed grades were excellent in three cases, good in three cases, and fair in one case. Muscle strength recovered to M5 in two cases, M4 in three cases, and showed no recovery in two cases. The pre-operative Majeed grades were good in five cases, fair in two cases, and poor in one case of the series without lumbosacral plexus injury, while the post-operative Majeed grades were excellent in seven cases and good in one case. CONCLUSION: APSJO through LRA may be a feasible strategy for treating pelvic fracture malunion and nonunion with promising application.

Transcriptome Analysis and Metabolic Profiling Reveal the Key Regulatory Pathways in Drought Stress Responses and Recovery in Tomatoes.

Drought stress is a major abiotic factor affecting tomato production and fruit quality. However, the genes and metabolites associated with tomato responses to water deficiency and rehydration are poorly characterized. To identify the functional genes and key metabolic pathways underlying tomato responses to drought stress and recovery, drought-susceptible and drought-tolerant inbred lines underwent transcriptomic and metabolomic analyses. A total of 332 drought-responsive and 491 rehydration-responsive core genes were robustly differentially expressed in both genotypes. The drought-responsive and rehydration-responsive genes were mainly related to photosynthesis-antenna proteins, nitrogen metabolism, plant-pathogen interactions, and the MAPK signaling pathway. Various transcription factors, including homeobox-leucine zipper protein ATHB-12, NAC transcription factor 29, and heat stress transcription factor A-6b-like, may be vital for tomato responses to water status. Moreover, 24,30-dihydroxy-12(13)-enolupinol, caffeoyl hawthorn acid, adenosine 5'-monophosphate, and guanosine were the key metabolites identified in both genotypes under drought and recovery conditions. The combined transcriptomic and metabolomic analysis highlighted the importance of 38 genes involved in metabolic pathways, the biosynthesis of secondary metabolites, the biosynthesis of amino acids, and ABC transporters for tomato responses to water stress. Our results provide valuable clues regarding the molecular basis of drought tolerance and rehydration. The data presented herein may be relevant for genetically improving tomatoes to enhance drought tolerance.

Effect of different lumbar-iliac fixation and sacral slope for Tile C1.3 pelvic fractures: a biomechanical study.

BACKGROUND: Lumbar-iliac fixation (LIF) is a common treatment for Tile C1.3 pelvic fractures, but different techniques, including L4-L5/L5 unilateral LIF (L4-L5/L5 ULIF), bilateral LIF (BLIF), and L4-L5/L5 triangular osteosynthesis (L4-L5/L5 TOS), still lack biomechanical evaluation. The sacral slope (SS) is key to the vertical shear of the sacrum but has not been investigated for its biomechanical role in lumbar-iliac fixation. The aim of this study is to evaluate the biomechanical effects of different LIF and SS on Tile C1.3 pelvic fracture under two-legged standing load in human cadavers. METHODS: Eight male fresh-frozen human lumbar-pelvic specimens were used in this study. Compressive force of 500 N was applied to the L4 vertebrae in the two-legged standing position of the pelvis. The Tile C1.3 pelvic fracture was prepared, and the posterior pelvic ring was fixed with L5 ULIF, L4-L5 ULIF, L5 TOS, L4-L5 TOS, and L4-L5 BLIF, respectively. Displacement and rotation of the anterior S1 foramen at 30° and 40° sacral slope (SS) were analyzed. RESULTS: The displacement of L4-L5/L5 TOS in the left-right and vertical direction, total displacement, and rotation in lateral bending decreased significantly, which is more pronounced at 40° SS. The difference in stability between L4-L5 and L5 ULIF was not significant. BLIF significantly limited left-right displacement. The ULIF vertical displacement at 40° SS was significantly higher than that at 30° SS. CONCLUSIONS: This study developed an in vitro two-legged standing pelvic model and demonstrated that TOS enhanced pelvic stability in the coronal plane and cephalad-caudal direction, and BLIF enhanced stability in the left-right direction. L4-L5 ULIF did not further improve the immediate stability, whereas TOS is required to increase the vertical stability at greater SS.

Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials.

BACKGROUND: Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours. METHODS: The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591. FINDINGS: We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55-85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9-11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (pinteraction=0·0019), higher volume of metastases (pinteraction=0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (pinteraction=0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (-1%, 95% CI -15 to 12, for progression-free survival; 0%, -10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival). INTERPRETATION: The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes. FUNDING: UK Medical Research Council and Prostate Cancer UK.

Acute toxicity comparison of magnetic resonance-guided adaptive versus fiducial or computed tomography-guided non-adaptive prostate stereotactic body radiotherapy: A systematic review and meta-analysis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is gaining wider adoption for prostate cancer management but there remain significant toxicity risks when delivering prostate SBRT with standard techniques. Magnetic resonance-guided daily adaptive SBRT (MRg-A-SBRT) offers technological advantages in precision of radiation dose delivery, but the toxicity profile associated with MRg-A-SBRT compared to more standardly used fiducial or computed tomography-guided non-adaptive prostate SBRT (CT-SBRT) remains unknown. METHODS: A meta-analysis to compare acute toxicity rates associated with MRg-A-SBRT and CT-SBRT for prostate cancer was performed in compliance with PRISMA guidelines. MEDLINE (PubMed) and Google Scholar were searched for prospective studies of prostate SBRT that were published between January 1, 2018 and August 31, 2022. Random effects and fixed effects models were used to estimate pooled toxicity rates, and meta-regression was performed to compare toxicity between MRg-A-SBRT and CT-SBRT study groups. RESULTS: Twenty-nine prospective studies were identified that met the inclusion criteria and included a total of 2547 patients. The pooled estimates for acute grade 2 or higher (G2+) genitourinary (GU) and gastrointestinal (GI) toxicity for MRg-A-SBRT were 16% (95% confidence interval [CI], 10%-24%) and 4% (95% CI, 2%-7%) and for CT-SBRT they were 28% (95% CI, 23%-33%) and 9% (95% CI, 6%-12%), respectively. On meta-regression, the odds ratios for acute G2+ GU and GI toxicities comparing MRg-A-SBRT and CT-SBRT were 0.56 (95% CI, 0.33-0.97, p = .04) and 0.40 (95% CI, 0.17-0.96, p = .04), respectively. CONCLUSION: MRg-A-SBRT is associated with a significantly reduced risk of acute G2+ GU or GI toxicity compared to CT-SBRT. Longer follow-up will be needed to evaluate late toxicity and disease control outcomes. PLAIN LANGUAGE SUMMARY: Magnetic resonance imaging-guided daily adaptive prostate stereotactic radiation (MRg-A-SBRT) is a treatment that may allow for delivery of prostate radiation more precisely than other radiotherapy techniques, but it is unknown whether this reduces side effects compared to standardly used computed tomography-guided SBRT (CT-SBRT). In this systematic review and meta-analysis combining data from 29 clinical trials including 2547 patients, it was found that the risk of short-term urinary side effects was reduced by 44% and the risk of short-term bowel side effects was reduced by 60% with MRg-A-SBRT compared to CT-SBRT.

Cu Tailoring Pt Enables Branched-Structured Electrocatalysts with High Concave Surface Curvature Toward Efficient Methanol Oxidation.

Surface engineering offers opportunities for the design and synthesis of Pt-based alloyed electrocatalysts with high mass activity and resistance to CO poisoning, which is of great significance for methanol electrooxidation. Surface curvature regulation may endow electrocatalysts with enhanced atomic utilization and abundance of unsaturated atoms; however, a reliable synthetic route for controlled construction of tailorable curved surface is still lacking. Here, a colloidal-chemical method to synthesize two types of PtCu branched-structured electrocatalysts, where the concave curvature can be customized is reported. These studies show that, among various synthesis parameters, the concentration of CuCl2 ·2H2 O precursor is the key factor in manipulating the reaction kinetics and determining the concave surface curvature. Significantly, PtCu branched nanocrystals with long and sharp arms (PtCu BNCs-L), featuring a high concave surface curvature, exhibit remarkable activity and stability toward MOR, which is mainly attributed to advanced features of a highly concave surface and the synergistically bifunctional effect from introduced oxophilic Cu metal. In situ Raman spectroscopy and CO stripping test demonstrates weakened CO adsorption and accelerated CO removal on PtCu BNCs-L. This work highlights the importance of surface curvature, opening up an appealing route for the design and synthesis of advanced electrocatalysts with well-defined surface configurations.

Anion Exchange Facilitates the In Situ Construction of Bi/BiO Interfaces for Enhanced Electrochemical CO2 -to-Formate Conversion Over a Wide Potential Window.

Electrochemical reduction of CO2 (CO2 RR) into value-added products is a promising strategy to reduce energy consumption and solve environmental issues. Formic acid/formate is one of the high-value, easy-to-collect, and economically viable products. Herein, the reconstructed Bi2 O2 CO3 nanosheets (BOCR NSs) are synthesized by an in situ electrochemical anion exchange strategy from Bi2 O2 SO4 as a pre-catalyst. The BOCR NSs achieve a high formate Faradaic efficiency (FEformate ) of 95.7% at -1.1 V versus reversible hydrogen electrode (vs. RHE), and maintain FEformate above 90% in a wide potential range from -0.8 to -1.5 V in H-cell. The in situ spectroscopic studies reveal that the obtained BOCR NSs undergo the anion exchange from Bi2 O2 SO4 to Bi2 O2 CO3 and further promote the self-reduction to metallic Bi to construct Bi/BiO active site to facilitate the formation of OCHO* intermediate. This result demonstrates anion exchange strategy can be used to rational design high performance of the catalysts toward CO2 RR.

NCR343 is required to maintain the viability of differentiated bacteroids in nodule cells in Medicago truncatula.

Bacteroid (name for rhizobia inside nodule cells) differentiation is a prerequisite for successful nitrogen-fixing symbiosis. In certain legumes, under the regulation of host proteins, for example, a large group of NCR (nodule cysteine rich) peptides, bacteroids undergo irreversible terminal differentiation. This process causes them to lose the ability to propagate inside nodule cells while boosting their competency for nitrogen fixation. How host cells maintain the viability of differentiated bacteroids while maximizing their nitrogen-reducing activities remains elusive. Here, through mutant screen, map-based cloning, and genetic complementation, we find that NCR343 is required for the viability of differentiated bacteroids. In Medicago truncatula debino1 mutant, differentiated bacteroids decay prematurely, and NCR343 is proved to be the casual gene for debino1. NCR343 is mainly expressed in the nodule fixation zone, where bacteroids are differentiated. In nodule cells, mature NCR343 peptide is secreted into the symbiosomes. RNA-Seq assay shows that many stress-responsive genes are significantly induced in debino1 bacteroids. Additionally, a group of stress response-related rhizobium proteins are identified as putative interacting partners of NCR343. In summary, our findings demonstrate that beyond promoting bacteroid differentiation, NCR peptides are also required in maintaining the viability of differentiated bacteroids.

The Medicago truncatula nodule-specific cysteine-rich peptides, NCR343 and NCR-new35 are required for the maintenance of rhizobia in nitrogen-fixing nodules.

In the nodules of IRLC legumes, including Medicago truncatula, nitrogen-fixing rhizobia undergo terminal differentiation resulting in elongated and endoreduplicated bacteroids specialized for nitrogen fixation. This irreversible transition of rhizobia is mediated by host produced nodule-specific cysteine-rich (NCR) peptides, of which c. 700 are encoded in the M. truncatula genome but only few of them have been proved to be essential for nitrogen fixation. We carried out the characterization of the nodulation phenotype of three ineffective nitrogen-fixing M. truncatula mutants using confocal and electron microscopy, monitored the expression of defence and senescence-related marker genes, and analysed the bacteroid differentiation with flow cytometry. Genetic mapping combined with microarray- or transcriptome-based cloning was used to identify the impaired genes. Mtsym19 and Mtsym20 mutants are defective in the same peptide NCR-new35 and the lack of NCR343 is responsible for the ineffective symbiosis of NF-FN9363. We found that the expression of NCR-new35 is significantly lower and limited to the transition zone of the nodule compared with other crucial NCRs. The fluorescent protein-tagged version of NCR343 and NCR-new35 localized to the symbiotic compartment. Our discovery added two additional members to the group of NCR genes essential for nitrogen-fixing symbiosis in M. truncatula.

Substrate and adenylate limit subtropical tree fine-root respiration under soil warming.

How root respiration acclimates to global warming remains unclear, especially in subtropical forests that play a key role in the global carbon budget. In a large-scale in situ soil warming experiment, the occurrence of, and mechanisms controlling over, the acclimation of fine-root respiration of Cunninghamia lanceolata during the fourth year of warming were investigated. Specific respiration rates (at reference temperature of 20°C; SRR20 ) were measured with exogenous glucose addition, uncoupler addition, or no addition, and root morphological and chemical traits were also measured. Warming decreased SRR20 by 18.4% only during summer, indicating partial thermal acclimation of fine-root respiration under warming. Warming did not change fine-root N concentration, showing no possible enzyme limitation on respiration. Warming decreased root soluble sugar/starch ratio in summer, and glucose addition increased respiration only under warming, indicating a warming-induced substrate limitation on respiration. Uncoupler addition also stimulated respiration only under warming, showing a warming-induced adenylate limitation on respiration. These findings suggest that thermal acclimation of root respiration in subtropical forests, which is at least partially constrained by substrate and adenylate use, is conducive to reducing ecosystem carbon emissions and mitigating the positive feedback between atmospheric CO2 and climate warming.