The heat shock factor 20-HSF4-cellulose synthase A2 module regulates heat stress tolerance in maize.

Temperature shapes the geographical distribution and behavior of plants. Understanding the regulatory mechanisms underlying the plant heat stress response is important for developing climate-resilient crops, including maize (Zea mays). To identify transcription factors (TFs) that may contribute to the maize heat stress response, we generated a dataset of short- and long-term transcriptome changes following a heat treatment time course in the inbred line B73. Co-expression network analysis highlighted several TFs, including the class B2a heat shock factor (HSF) ZmHSF20. Zmhsf20 mutant seedlings exhibited enhanced tolerance to heat stress. Furthermore, DNA affinity purification sequencing and Cleavage Under Targets and Tagmentation assays demonstrated that ZmHSF20 binds to the promoters of Cellulose synthase A2 (ZmCesA2) and three class A Hsf genes, including ZmHsf4, repressing their transcription. We showed that ZmCesA2 and ZmHSF4 promote the heat stress response, with ZmHSF4 directly activating ZmCesA2 transcription. In agreement with the transcriptome analysis, ZmHSF20 inhibited cellulose accumulation and repressed the expression of cell wall-related genes. Importantly, the Zmhsf20 Zmhsf4 double mutant exhibited decreased thermotolerance, placing ZmHsf4 downstream of ZmHsf20. We proposed an expanded model of the heat stress response in maize, whereby ZmHSF20 lowers seedling heat tolerance by repressing ZmHsf4 and ZmCesA2, thus balancing seedling growth and defense.

Phase 1b Trial Evaluating Tolerability and Activity of Targeted Fibroblast Growth Factor Receptor Inhibition in Localized Upper Tract Urothelial Carcinoma.

PURPOSE: We initiated a biomarker-informed preoperative study of infigratinib, a fibroblast growth factor receptor (FGFR) inhibitor, in patients with localized upper tract urothelial carcinoma (UTUC), a population with high unmet needs and tumor with a high frequency of FGFR3 alterations. MATERIALS AND METHODS: Patients with localized UTUC undergoing ureteroscopy or nephroureterectomy/ureterectomy were enrolled on a phase 1b trial (NCT04228042). Once-daily infigratinib 125 mg by mouth × 21 days (28-day cycle) was given for 2 cycles. Tolerability was monitored by Bayesian design and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, done after endoscopic biopsy and post-trial surgery. Total planned enrollment: 20 patients. Targeted sequencing performed using a NovaSeq 6000 solid tumor panel. RESULTS: From May 2021 to November 2022, 14 patients were enrolled, at which point the trial was closed due to termination of all infigratinib oncology trials. Two patients (14.3%) had treatment-terminating toxicities, well below the stopping threshold. Responses occurred in 6 (66.7%) of 9 patients with FGFR3 alterations. Responders had median tumor size reduction of 67%, with 3 of 5 patients initially planned for nephroureterectomy/ureterectomy converted to ureteroscopy. Median follow-up in responders was 24.7 months (14.9-28.9). CONCLUSIONS: In this first trial of targeted therapy for localized UTUC, FGFR inhibition was well tolerated and had significant activity in FGFR3 altered tumors. Renal preservation was enabled in a substantial proportion of participants. These data support the design of a biomarker-driven phase 2 trial of FGFR3 inhibition in this population with significant unmet clinical needs.

Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged ≥4 to <8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR).

OBJECTIVE: Delandistrogene moxeparvovec is approved in the USA for the treatment of ambulatory patients (4-5 years) with Duchenne muscular dystrophy. ENDEAVOR (SRP-9001-103; NCT04626674) is a single-arm, open-label study to evaluate delandistrogene moxeparvovec micro-dystrophin expression, safety, and functional outcomes following administration of commercial process delandistrogene moxeparvovec. METHODS: In cohort 1 of ENDEAVOR (N = 20), eligible ambulatory males, aged ≥4 to <8 years, received a single intravenous infusion of delandistrogene moxeparvovec (1.33 × 1014 vg/kg). The primary endpoint was change from baseline (CFBL) to week 12 in delandistrogene moxeparvovec micro-dystrophin by western blot. Additional endpoints evaluated included: safety; vector genome copies; CFBL to week 12 in muscle fiber-localized micro-dystrophin by immunofluorescence; and functional assessments, including North Star Ambulatory Assessment, with comparison with a propensity score-weighted external natural history control. RESULTS: The 1-year safety profile of commercial process delandistrogene moxeparvovec in ENDEAVOR was consistent with safety data reported in other delandistrogene moxeparvovec trials (NCT03375164 and NCT03769116). Delandistrogene moxeparvovec micro-dystrophin expression was robust, with sarcolemmal localization at week 12; mean (SD) CFBL in western blot, 54.2% (42.6); p < 0.0001. At 1 year, patients demonstrated stabilized or improved North Star Ambulatory Assessment total scores; mean (SD) CFBL, +4.0 (3.5). Treatment versus a propensity score-weighted external natural history control demonstrated a statistically significant difference in least squares mean (standard error) CFBL in North Star Ambulatory Assessment, +3.2 (0.6) points; p < 0.0001. INTERPRETATION: Results confirm efficient transduction of muscle by delandistrogene moxeparvovec. One-year post-treatment, delandistrogene moxeparvovec was well tolerated, and demonstrated stabilized or improved motor function, suggesting a clinical benefit for patients with Duchenne muscular dystrophy. ANN NEUROL 2023;94:955-968.

Exploring the pyro-phototronic effect for giant lateral photoresponse in an ITO/CdS/Si heterojunction position-sensitive detector.

The demand for a high-performance position sensitive detector (PSD), a novel type of photoelectric sensor, is increasing due to advancements in digitization and automation technology. Cadmium sulfide (CdS), a non-centrosymmetric material, holds significant potential in photoelectric devices. However, the pyroelectric effect of CdS in PSDs and its influence on lateral photoresponse are still unknown. In this work, we fabricated an ITO/CdS/Si heterojunction using chemical bath deposition (CBD) and investigated the pyro-phototronic effect under nonuniform illumination. The theory of electron-hole pairs' generation, separation, and carrier diffusion was carefully considered to understand the underlying mechanisms. Our experimental findings revealed that the device exhibited an exceptionally high position sensitivity (PS) of 1061.3 mV/mm, surpassing the generally observed PS of 655.1 mV/mm induced by single photovoltaic effect by 160.5%. Meanwhile, the PSD demonstrated rapid response times of 0.01 and 0.04 ms, respectively. Moreover, the influence of ambient temperature and electrode distance on the pyro-phototronic effect was well analyzed. Notably, the PSD exhibited remarkable stability even at ambient temperatures up to 150 °C. Despite the considerable working distance of 11 mm, the PS of the PSD remained at 128.99 mV/mm. These findings provide valuable theoretical and experimental foundations for optimizing the design and implementation of high-performance large working distance PSDs.

Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial.

INTRODUCTION/AIMS: Delandistrogene moxeparvovec is indicated in the United States for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. Long-term delandistrogene moxeparvovec microdystrophin protein (a shortened dystrophin that retains key functional domains of the wild-type protein) expression may positively alter disease progression in patients with DMD. We evaluated long-term safety and functional outcomes of delandistrogene moxeparvovec in patients with DMD. METHODS: An open-label, phase 1/2a, nonrandomized controlled trial (Study 101; NCT03375164) enrolled ambulatory males, ≥4 to <8 years old, with DMD. Patients received a single intravenous infusion (2.0 × 1014 vg/kg by supercoiled quantitative polymerase chain reaction) of delandistrogene moxeparvovec and prednisone (1 mg/kg/day) 1 day before to 30 days after treatment. The primary endpoint was safety. Functional outcomes were change from baseline in North Star Ambulatory Assessment (NSAA) and timed function tests. RESULTS: Four patients (mean age, 5.1 years) were enrolled. There were 18 treatment-related adverse events; all occurred within 70 days posttreatment and resolved. Mean NSAA total score increased from 20.5 to 27.5, baseline to year 4, with a mean (standard deviation) change of +7.0 (2.9). Post hoc analysis demonstrated a statistically significant and clinically meaningful 9-point difference in NSAA score, relative to a propensity-score-weighted external control cohort (least-squares mean [standard error] = 9.4 [3.4]; P = .0125). DISCUSSION: Gene transfer therapy with delandistrogene moxeparvovec treatment is well tolerated, with a favorable safety profile. Functional improvements are sustained through 4 years, suggesting delandistrogene moxeparvovec may positively alter disease progression.

Efbemalenograstim alfa not inferior to pegfilgrastim in providing neutrophil support in women with breast cancer undergoing myelotoxic chemotherapy: results of a phase 2 randomized, multicenter, open-label trial.

PURPOSE: Evaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2, dose-finding, open-label study (NCT01648322, ClinicalTrials.gov, 2012-07-19). METHODS: 232 patients received up to 4 cycles of chemotherapy, 141 patients with docetaxel + cyclophosphamide (TC) and 91 patients with docetaxel + doxorubicin + cyclophosphamide (TAC). Patients were randomized to efbemalenograstim alfa (80, 240, or 320 µg/kg [TC]; 240 or 320 µg/kg [TAC]) or pegfilgrastim (6 mg) on Day 2 of each cycle. RESULTS: Efbemalenograstim alfa was non-inferior to pegfilgrastim in duration of moderate and severe neutropenia (absolute neutrophil count [ANC] < 1.0 × 109/L) in TAC Cycle 1 (mean [SD] of 2.1 [1.58] and 2.1 [1.46] days for 240 µg/kg and 320 µg/kg efbemalenograstim alfa, respectively, and 1.8 [1.28] days for pegfilgrastim), with a difference (95% CI) of 0.3 (-0.4, 1.1) days. ANC nadir occurred between Days 7-8 of TAC Cycle 1, with mean [SD] of 0.68 [1.064], 0.86 [1.407] and 0.78[1.283] × 109/L for 240 µg/kg, 320 µg/kg efbemalenograstim alfa and pegfilgrastim, respectively. Time to ANC recovery post nadir (defined as an ANC > 2.0 × 109/L after the expected ANC nadir) was 2.0-2.4 and 1.9 days for TAC patients treated with efbemalenograstim alfa and pegfilgrastim, respectively. No significant difference was found between any dose of efbemalenograstim alfa and pegfilgrastim in TAC Cycle 1 for incidence of moderate to severe neutropenia (76%-77% of patients) or incidence of severe neutropenia (ANC < 0.5 × 109/L; 63%-72%). Efbemalenograstim alfa exhibited similar safety profile to pegfilgrastim. Febrile neutropenia occurred in 4 (1.8%) patients, 2 patients each for 320 µg/kg efbemalenograstim alfa and pegfilgrastim, with no event considered related to study drug. CONCLUSION: Efbemalenograstim alfa was comparable to pegfilgrastim in efficacy and safety. GOV IDENTIFIER: NCT01648322.

Enhancing iron content and growth of cucumber seedlings with MgFe-LDHs under low-temperature stress.

The development of cost-effective and eco-friendly fertilizers is crucial for enhancing iron (Fe) uptake in crops and can help alleviate dietary Fe deficiencies, especially in populations with limited access to meat. This study focused on the application of MgFe-layered double hydroxide nanoparticles (MgFe-LDHs) as a potential solution. We successfully synthesized and characterized MgFe-LDHs and observed that 1-10 mg/L MgFe-LDHs improved cucumber seed germination and water uptake. Notably, the application of 10 mg/L MgFe-LDHs to roots significantly increased the seedling emergence rate and growth under low-temperature stress. The application of 10 mg/L MgFe-LDHs during sowing increased the root length, lateral root number, root fresh weight, aboveground fresh weight, and hypocotyl length under low-temperature stress. A comprehensive analysis integrating plant physiology, nutrition, and transcriptomics suggested that MgFe-LDHs improve cold tolerance by upregulating SA to stimulate CsFAD3 expression, elevating GA3 levels for enhanced nitrogen metabolism and protein synthesis, and reducing levels of ABA and JA to support seedling emergence rate and growth, along with increasing the expression and activity of peroxidase genes. SEM and FTIR further confirmed the adsorption of MgFe-LDHs onto the root hairs in the mature zone of the root apex. Remarkably, MgFe-LDHs application led to a 46% increase (p < 0.05) in the Fe content within cucumber seedlings, a phenomenon not observed with comparable iron salt solutions, suggesting that the nanocrystalline nature of MgFe-LDHs enhances their absorption efficiency in plants. Additionally, MgFe-LDHs significantly increased the nitrogen (N) content of the seedlings by 12% (p < 0.05), promoting nitrogen fixation in the cucumber seedlings. These results pave the way for the development and use of LDH-based Fe fertilizers.

Identification of Xuanfei Baidu granule constituents by liquid chromatography-quadruple-time-of-flight-mass spectrometry and its anti-inflammatory active constituents using a lipopolysaccharide-induced RAW264.7 cell model.

The Xuanfei Baidu (XFBD) prescription, a traditional Chinese medicine prescription, has demonstrated significant anti-inflammatory activities; however, the number of its reported constituents is limited, and its anti-inflammatory constituents are unclear. In this study, the constituents of XFBD granule, a granule dosage of XFBD prescription, were thoroughly examined in vitro and in vivo using liquid chromatography-quadruple-time-of-flight-mass spectrometry, and the anti-inflammatory constituents were screened. A total of 214 constituents were identified from the XFBD granule, 62 of which were confirmed via comparison with reference standards. After intragastric administration of XFBD granule, 63 and 28 constituents were absorbed into the rat sera and lungs in prototype form, respectively. XFBD granule and XFBD-containing serum were found to significantly reduce nitric oxide (NO) and interleukin-6 (IL-6) secretion in lipopolysaccharide-induced RAW264.7 cells. Five anti-inflammatory constituents (verbasoside, scutellarin, luteolin, apigenin, and pogostone) were found to reduce the concentration of NO and IL-6 in a dose-dependent manner. Moreover, the combination of these five constituents could significantly reduce NO secretion even when the concentration of each constituent was two to three orders of magnitude lower than their individual minimum effective concentrations. Overall, this study provides a valuable reference for the discovery of effective constituents from the XFBD granule.

Knowledge, attitude, and practice of healthcare professionals toward cognitive dysfunction in Parkinson's disease and cognitive rehabilitation.

BACKGROUND: To investigate the knowledge, attitude, and practice (KAP) of healthcare professionals regarding cognitive dysfunction and cognitive rehabilitation in Parkinson's disease (PD). METHODS: This multicenter, cross-sectional survey enrolled physicians and nurses in 10 hospitals between October 2022 and November 2022. A self-administered questionnaire was developed to collect the demographic information of the participants and their knowledge, attitude, and practice toward cognitive dysfunction in PD and cognitive rehabilitation. RESULTS: This study enrolled 224 physicians and 229 nurses. The knowledge, attitude, and practice scores were 12.57 ± 3.76 (total score: 22), 29.10 ± 3.71 (total score: 32), and 21.07 ± 8.03 (total score: 28) among physicians, and 9.97 ± 4.70 (total score: 22), 25.27 ± 8.96 (total score: 32), and 25.27 ± 8.96 (total score: 28) among nurses. Among physicians, the knowledge scores (OR = 4.23, 95%CI: 2.36-7.58, P < 0.001) and attitude scores (OR = 3.00, 95%CI: 1.67-5.37, P < 0.001) were independently associated with good practice. Among nurses, the knowledge scores (OR = 4.31, 95%CI: 2.31-8.05, P < 0.001), attitude scores (OR = 5.18, 95%CI: 2.82-9.53, P < 0.001), working department (Ref: rehabilitation; neurology: OR = 2.26, 95%CI: 1.01-5.08, P = 0.048; public health service/chronic disease follow-up center: OR = 2.98, 95%CI: 1.12-7.92, P = 0.028) were independently associated with good practice. CONCLUSIONS: Physicians and nurses have insufficient knowledge, favorable attitudes, and active practice regarding cognitive dysfunction and cognitive rehabilitation in PD. This study identified gaps in KAP and suggested education activities to improve the KAP toward cognitive dysfunction in PD.

Multi-Carrier Generation in Organic-Passivated Black Silicon Solar Cells with Industrially Feasible Processes.

The innate inverse Auger effect within bulk silicon can result in multiple carrier generation. Observation of this effect is reliant upon low high-energy photon reflectance and high-quality surface passivation. In the photovoltaics industry, metal-assisted chemical etching (MACE) to afford black silicon (b-Si) can provide a low high-energy photon reflectance. However, an industrially feasible and cheaper technology to conformally passivate the outer-shell defects of these nanowires is currently lacking. Here, a technology is introduced to infiltrate black silicon nanopores with a simple and vacuum-free organic passivation layer that affords millisecond-level minority carrier lifetimes and matches perfectly with existing solution-based processing of the MACE black silicon. Advancements such as the demonstration of an excellent passivation effect whilst also being low reflectance provide a new technological route for inverse Auger multiple carrier generation and an industrially feasible technical scheme for the development of the MACE b-Si solar cells.

Efficacy and safety of Oral LL-37 against the Omicron BA.5.1.3 variant of SARS-COV-2: A randomized trial.

Recombinant LL-37 Lactococcus lactis (Oral LL-37) was designed to prevent progression of COVID-19 by targeting virus envelope, however, effectiveness and safety of Oral LL-37 in clinical application was unclear. A total of 238 adult inpatients, open-labelled, randomized, placebo-controlled, single-center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS-CoV-2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL-37 could significantly shorten NCT (LL-37 9.80 ± 2.67 vs. placebo 14.04 ± 5.89, p < 0.01). For Oral LL-37, as early as treated in 6 days, the adjusted hazard ratio (HR) for a primary event of nucleic acid negative outcome was 6.27-fold higher than 7-day-later (HR: 6.276, 95% confidence interval [CI]: 3.631-10.848, p < 0.0001), and the adjusted HR of Oral LL-37 within 6 days is higher than placebo (HR: 2.427 95% CI: 1.239-4.751, p = 0.0097). No severe AEs were observed during hospitalization and follow-up investigation. This study shows that early intervention of Oral LL-37 incredibly reduces NCT implying a potential for clearance of Omicron BA.5.1.3 without evident safety concerns.

Two-Dimensional Lanthanide Metal-Organic Frameworks as a Platform for Sensing Pollutant and Nitrophenols Reduction.

The discharge of harmful and toxic pollutants in water is destroying the ecosystem balance and human being health at an alarming rate. Therefore, the detection and removal of water pollutants by using stable and efficient materials are significant but challenging. Herein, three novel lanthanide metal-organic frameworks (Ln-MOFs), [La(L)(DMF)2(H2O)2]·H2O (LCUH-104), [Nd(L)(DMF)2(H2O)2]·H2O (LCUH-105), and [Pr(L)(DMF)2(H2O)2]·H2O (LCUH-106) [H3L = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid (H3TZI)] were solvothermally constructed and structurally characterized. In the three Ln-MOFs, dinuclear metallic clusters {Ln2} were connected by deprotonated tetrazol-containing dicarboxylate TZI3- to obtain a 2D layered framework with a point symbol of {42·84}·{46}. Their excellent chemical and thermal stabilities were beneficial to carry out fluorescence sensing and achieve the catalytic nitrophenols (NPs) reduction. Especially, the incorporation of the nitrogen-rich tetrazole ring into their 2D layered frameworks enables the fabrication of Pd nanocatalysts (Pd NPs@LCUH-104/105/106) and have dramatically enhanced catalytic activity by using the unique metal-support interactions between three Ln-MOFs and the encapsulating palladium nanoparticles (Pd NPs). Specifically, the reduction of NPs (2-NP, 3-NP, and 4-NP) in aqueous solution by Pd NPs@LCUH-104 exhibits exceptional conversion efficiency, remarkable rate constants (k), and outstanding cycling stability. The catalytic rate of Pd NPs@LCUH-104 for 4-NP is nearly 8.5 times more than that of Pd/C (wt 5%) and its turnover frequency value is 0.051 s-1, which indicate its excellent catalytic activity. Meanwhile, LCUH-105, as a multifunctional fluorescence sensor, exhibited excellent fluorescence detection of norfloxacin (NFX) (turn on) and Cr2O72- (turn off) with high selectivity and sensitivity at a low concentration, and the corresponding fluorescence enhancement/quenching mechanism has also been systematically investigated through various detection means and theoretical calculations.

Series of Dual Functional Two-Dimensional RE-OFs for Nitrophenol Reduction and Dye Separation.

The rational design and preparation of stable and multifunctional metal-organic frameworks (MOFs) with excellent catalysis and adsorption properties are desirable but are great challenges. The nitrophenol (NP) reduction to aminophenols (APs) by using the catalyst Pd@MOFs is an effective strategy, which has attracted extensive attention in recent years. Here, we report four stable isostructural two-dimensional (2D) rare earth metal-organic frameworks [RE4(AAPA)6(DMA)2 (H2O)4][DMA]3[H2O]8 (namely LCUH-101, RE = Eu, Gd, Tb, Y; AAPA2- = 5-[(anthracen-9-yl-methyl)-amino]-1,3-isophthalate), which feature a 2D layer structure with sql topology of point symbol {44·62} and exhibit excellent chemical stability and thermostability. The as-synthesized Pd@LCUH-101 was utilized for the catalytic reduction of 2/3/4-nitrophenol, which indicates high catalytic activity and recyclability attributed to the synergistic effect between Pd nanoparticles and the 2D layered structure. Of note, the turnover frequency (TOF), the reaction rate constant (k), and the activation energy (Ea) of Pd@LCUH-101 (Eu) in the reduction of 4-NP, respectively, are 1.09 s-1, 2.17 min-1, and 50.2 kJ·mol-1, which show that it has superior catalytic activity. Remarkably, LCUH-101 (Eu, Gd, Tb, and Y) are multifunctional MOFs that can effectively absorb and separate mixed dyes. The appropriate interlayer spacing enables them to efficiently adsorb methylene blue (MB) and rhodamine B (RhB) in aqueous solution, with adsorption capacities of 0.97 and 0.41 g·g-1, respectively, which is one of the highest values among those of the reported MOF-based adsorbers. Meanwhile, LCUH-101 (Eu) can be used for the separation of the dye mixture MB/MO and RhB/MO, and the excellent reusability enables LCUH-101 (Eu) to be used as chromatographic column filters to quickly separate and recover dyes. Therefore, this work provides a new strategy for the exploitation of stable and efficient catalysts for NP reduction and adsorbents for dyes.

Efbemalenograstim alfa, an Fc fusion protein, long-acting granulocyte-colony stimulating factor for reducing the risk of febrile neutropenia following chemotherapy: results of a phase III trial.

PURPOSE: Evaluate the safety and efficacy of efbemalenograstim alfa for reducing the risk of febrile neutropenia in breast cancer patients undergoing myelosuppressive chemotherapy. METHODS: A phase III, randomized, double-blind, placebo-controlled study was conducted. A total of 122 subjects received up to 4 cycles of TA chemotherapy (75 mg/m2 docetaxel + 60 mg/m2 doxorubicin). Patients were randomized in a 2:1 ratio to subcutaneously inject a single 20 mg of efbemalenograstim alfa or placebo on day 2 of cycle 1, and all subjects received efbemalenograstim alfa on day 2 of cycles 2, 3, and 4. Duration of severe (grade 4) neutropenia (DSN), depth of neutrophil nadir, incidence of febrile neutropenia (FN), time to neutrophil recovery, and safety information were recorded. RESULTS: For the primary endpoint, the mean DSN in cycle 1 was 1.3 days and 3.9 days for efbemalenograstim alfa and placebo respectively (95% CI, 2.3, 3.4). As the lower bound of the 95% CI was > 0, superiority of efbemalenograstim alfa over placebo can be declared. In addition, the incidence of FN in Cycle 1 was lower in efbemalenograstim alfa group than in placebo group (4.8% vs. 25.6%; p = 0.0016). Patients in the efbemalenograstim alfa group required less intravenous antibiotics (3.6% vs. 17.9%; p = 0.0119). Most adverse events were consistent with those expected for breast cancer patient receiving TA chemotherapy. CONCLUSION: Efbemalenograstim alfa is effective and safe for significantly decreasing the duration of severe neutropenia and the incidence of febrile neutropenia in breast cancer patients who are receiving TA chemotherapy. TRIAL REGISTRATION: NCT02872103, August 19, 2016.

Multifeature analyses of vascular cambial cells reveal longevity mechanisms in old Ginkgo biloba trees.

Aging is a universal property of multicellular organisms. Although some tree species can live for centuries or millennia, the molecular and metabolic mechanisms underlying their longevity are unclear. To address this, we investigated age-related changes in the vascular cambium from 15- to 667-y-old Ginkgo biloba trees. The ring width decreased sharply during the first 100 to 200 y, with only a slight change after 200 y of age, accompanied by decreasing numbers of cambial cell layers. In contrast, average basal area increment (BAI) continuously increased with aging, showing that the lateral meristem can retain indeterminacy in old trees. The indole-3-acetic acid (IAA) concentration in cambial cells decreased with age, whereas the content of abscisic acid (ABA) increased significantly. In addition, cell division-, cell expansion-, and differentiation-related genes exhibited significantly lower expression in old trees, especially miR166 and HD-ZIP III interaction networks involved in cambial activity. Disease resistance-associated genes retained high expression in old trees, along with genes associated with synthesis of preformed protective secondary metabolites. Comprehensive evaluation of the expression of genes related to autophagy, senescence, and age-related miRNAs, together with analysis of leaf photosynthetic efficiencies and seed germination rates, demonstrated that the old trees are still in a healthy, mature state, and senescence is not manifested at the whole-plant level. Taken together, our results reveal that long-lived trees have evolved compensatory mechanisms to maintain a balance between growth and aging processes. This involves continued cambial divisions, high expression of resistance-associated genes, and continued synthetic capacity of preformed protective secondary metabolites.

Characterization of a novel marine microbial uricase from Priestia flexa and evaluation of the effects of CMCS conjugation on its enzymatic properties.

A novel uricase producing marine bacterium Priestia flexa alkaAU was isolated and identified. The 16S rDNA and the uricase coding gene were sequenced, analyzed and submitted to GenBank. The uricase from Priestia flexa alkaAU (PFU) was purified, determined to be 58.87 kDa, and conjugated with carboxymethyl chitosan (CMCS) by ionic gelation. CMCS conjugation had no effect on the optimum pH of PFU but decreased the optimum temperature by 10 °C. CMCS conjugation increased the specific activity of PFU by 53% at the human body temperature (37 °C) and small intestine's pH (pH 6.8). Uricase thermostabilizing ability of CMCS was significant in the range of 37-80 °C but not at lower temperatures. For improvement of the pH stability of PFU, CMCS was more effective at pHs 3-5 than pHs 6-11. CMCS increased the half-life of PFU against artificial intestinal fluid by 1.5 folds, which demonstrated the potential capability of CMCS-PFU for oral administration.

Co0 -Coδ+ Interface Double-Site-Mediated C-C Coupling for the Photothermal Conversion of CO2 into Light Olefins.

Solar-driven CO2 hydrogenation into multi-carbon products is a highly desirable, but challenging reaction. The bottleneck of this reaction lies in the C-C coupling of C1 intermediates. Herein, we construct the C-C coupling centre for C1 intermediates via the in situ formation of Co0 -Coδ+ interface double sites on MgAl2 O4 (Co-CoOx /MAO). Our experimental and theoretical prediction results confirmed the effective adsorption and activation of CO2 by the Co0 site to produce C1 intermediates, while the introduction of the electron-deficient state of Coδ+ can effectively reduce the energy barrier of the key CHCH* intermediates. Consequently, Co-CoOx /MAO exhibited a high C2-4 hydrocarbons production rate of 1303 µmol g-1 h-1 ; the total organic carbon selectivity of C2-4 hydrocarbons is 62.5 % under light irradiation with a high ratio (≈11) of olefin to paraffin. This study provides a new approach toward the design of photocatalysts used for CO2 conversion into C2+ products.

Ultrahigh Power Factor and Ultralow Thermal Conductivity at Room Temperature in PbSe/SnSe Superlattice: Role of Quantum-Well Effect.

Reduced dimension is one of the effective strategies to modulate thermoelectric properties. In this work, n-type PbSe/SnSe superlattices with quantum-well (QW) structure are fabricated by pulsed laser deposition. Here, it is demonstrated that the PbSe/SnSe multiple QW (MQW) shows a high power factor of ≈25.7 µW cm-1 K-2 at 300 K, four times larger than that of PbSe single layers. In addition, thermal conductivity falls below 0.32 ± 0.06 W m-1 K-1 due to the phonon scattering at interface when the PbSe well thickness is confined within the scale of phonon mean free path (1.8 nm). Featured with ultrahigh power factor and ultralow thermal conductivity, ZT at room temperature is significantly increased from 0.14 for PbSe single layer to 1.6 for PbSe/SnSe MQW.

Inflammation-Stimulated MSC-Derived Small Extracellular Vesicle miR-27b-3p Regulates Macrophages by Targeting CSF-1 to Promote Temporomandibular Joint Condylar Regeneration.

Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have been extensively studied in recent years. sEV contents change with the secreting cell state. When MSCs are exposed to an inflammatory environment, they release more functional growth factors, exosomes, and chemokines. Herein, MSCs are stimulated to alter sEV cargos and functions to regulate the inflammatory microenvironment and promote tissue regeneration. Sequencing of sEV miRNAs shows that certain RNAs conducive to cell function are upregulated. In this study, in vitro cell function experiments show that both inflammation-stimulated adipose-derived MSC (ADSC)-derived sEV (IAE) and normal ADSC-derived sEV (AE) promote cell proliferation; IAE also significantly improves cell migration. Regarding macrophage polarization regulation, IAE significantly promotes M2 macrophage differentiation. RNA-sequencing analysis indicates that high miR-27b-3p expression levels in IAE may regulate macrophages by targeting macrophage colony-stimulating factor-1 (CSF-1). In vivo, a rabbit temporomandibular joint (TMJ) condylar osteochondral defect model shows that both AE and IAE promote TMJ regeneration, with IAE having the most significant therapeutic effect. Therefore, the authors confirm that exposing MSCs to an inflammatory environment can feasibly enhance sEV functions and that modified sEVs achieve better therapeutic effects.

Greatly improved photoresponse in the MAPbBr3/Si heterojunction by introducing an ITO layer and optimizing MAPbBr3 layer thickness.

In this paper, a CH3NH3(MA)PbBr3/Si heterojunction photodetector (PD) is prepared, and a simple method is proposed to improve the performance by introducing an ITO conductive layer and modulating thickness of the MAPbBr3 layer. The results indicate that the MAPbBr3/Si heterojunction PD exhibits an ultra-broadband photoresponse ranging from 405 to 1064 nm, and excellent performances with the responsivity (R) of 0.394 mA/W, detectivity (D) of 0.11×1010 Jones, and response times of ∼2176/∼257 ms. When adding the ITO layer, the R and D are greatly improved to 0.426 A/W and 5.17×1010 Jones, which gets an increment of 1.08×105% and 4.7×103%, respectively. Meanwhile, the response times are reduced to ∼130/∼125 ms, and a good environmental stability is obtained. Moreover, it is found that the photoresponse is strongly dependent on the thickness of the MAPbBr3 layer. By modulating the MAPbBr3 layer thickness from ∼85 to ∼590 nm, the performances are further improved with the best R of ∼0.87 A/W, D of ∼1.92×1011 Jones, and response times of ∼129/∼130 ms achieved in the ∼215 nm-thick PD.