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The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective 1 , 2 . This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury 2 , 3 . Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 – 12 . However, how neuro–immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the Na V 1.8 nociceptor impairs skin wound repair and muscle regeneration after acute tissue injury. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process. CGRP acts via receptor activity-modifying protein 1 (RAMP1) on neutrophils, monocytes and macrophages to inhibit recruitment, accelerate death, enhance efferocytosis and polarize macrophages towards a pro-repair phenotype. The effects of CGRP on neutrophils and macrophages are mediated via thrombospondin-1 release and its subsequent autocrine and/or paracrine effects. In mice without nociceptors and diabetic mice with peripheral neuropathies, delivery of an engineered version of CGRP accelerated wound healing and promoted muscle regeneration. Harnessing neuro–immune interactions has potential to treat non-healing tissues in which dysregulated neuro–immune interactions impair tissue healing. Experiments in mouse models show that Na V 1.8 +  nociceptors innervate sites of injury and provide wound repair signals to immune cells by releasing calcitonin gene-related peptide (CGRP).

This paper studies an integrated optimization problem on quay crane and yard truck scheduling in container terminals. A mixed-integer programming model is formulated. For the model, we show the integrated scheduling problem is strongly NP-hard and investigate some properties that can considerably reduce the computational complexity. For solving the proposed model within a reasonable time, a particle swarm optimization based solution method is developed. Numerical experiments are conducted to compare the proposed method with the CPLEX solver and the genetic algorithm. The results validate the effectiveness of the proposed model and the efficiency of the proposed solution method.

Marker-assisted selection (MAS) refers to the use of molecular markers to assist phenotypic selections in crop improvement. Several types of molecular markers, such as single nucleotide polymorphism (SNP), have been identified and effectively used in plant breeding. The application of next-generation sequencing (NGS) technologies has led to remarkable advances in whole genome sequencing, which provides ultra-throughput sequences to revolutionize plant genotyping and breeding. To further broaden NGS usages to large crop genomes such as maize and wheat, genotyping-by-sequencing (GBS) has been developed and applied in sequencing multiplexed samples that combine molecular marker discovery and genotyping. GBS is a novel application of NGS protocols for discovering and genotyping SNPs in crop genomes and populations. The GBS approach includes the digestion of genomic DNA with restriction enzymes followed by the ligation of barcode adapter, PCR amplification and sequencing of the amplified DNA pool on a single lane of flow cells. Bioinformatic pipelines are needed to analyze and interpret GBS datasets. As an ultimate MAS tool and a cost-effective technique, GBS has been successfully used in implementing genome-wide association study (GWAS), genomic diversity study, genetic linkage analysis, molecular marker discovery and genomic selection under a large scale of plant breeding programs.

A previous phase 2 trial showed promising outcomes for patients with HER2-positive early-stage breast cancer using neoadjuvant de-escalation chemotherapy with paclitaxel, trastuzumab, and pertuzumab. We aimed to evaluate the efficacy of weekly nab-paclitaxel compared with the standard regimen of docetaxel plus carboplatin, both with trastuzumab and pertuzumab, as neoadjuvant therapies for patients with HER2-positive breast cancer. HELEN-006 was a multicentre, randomised, phase 3 trial done at six hospitals in China. We enrolled patients aged 18–70 years with untreated, histologically confirmed stage II–III invasive HER2-positive breast cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1. Using an interactive response system, patients were randomly assigned (1:1) under a permuted block randomisation scheme (block size of four), stratified by tumour stage, nodal status, and hormone receptor status. Patients received either intravenous nab-paclitaxel (125 mg/m2 on days 1, 8, and 15) for six 3-week cycles, or intravenous docetaxel (75 mg/m2 on day 1) plus intravenous carboplatin (area under the concentration-time curve 6 mg/mL per min on day 1) for six 3-week cycles. Both groups also received concurrent intravenous trastuzumab, with an initial loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg on day 1, as well as intravenous pertuzumab with a loading dose of 840 mg and a maintenance dose of 420 mg on day 1. This report is the final analysis of the primary endpoint, pathological complete response (ypT0/is ypN0), analysed in all patients who started treatment (modified intention to treat). The trial is registered with ClinicalTrials.gov, NCT04547907, and follow-up of the adjuvant phase is ongoing. Between Sept 20, 2020, and March 1, 2023, 789 patients were screened for eligibility, 689 of whom were randomly assigned (343 to the nab-paclitaxel group and 346 to the docetaxel plus carboplatin group). All 689 patients were Asian women. 669 patients received at least one dose of the study treatment and were included in the full analysis set (332 in the nab-paclitaxel group and 337 in the docetaxel plus carboplatin group). Median age of the patients was 50 years (IQR 43–55). Median follow-up time was 26 months (IQR 19–32). 220 (66·3% [95% CI 61·2–71·4]) patients in the nab-paclitaxel group had a pathological complete response, compared with 194 (57·6% [52·3–62·9]) in the docetaxel plus carboplatin group (combined odds ratio 1·54 [95% CI 1·10–2·14]; stratified p=0·011). 100 (30%) patients in the nab-paclitaxel group and 128 (38%) in the docetaxel plus carboplatin group had grade 3–4 adverse events. The most common grade 3–4 adverse events were nausea (22 [7%] in the nab-paclitaxel group vs 76 [23%] in the docetaxel plus carboplatin group), diarrhoea (25 [8%] vs 55 [16%]), and neuropathy (43 [13%] vs eight [2%]). Serious drug-related adverse events were reported in three (1%) patients in the nab-paclitaxel group and five (2%) in the docetaxel plus carboplatin group. No treatment-related deaths were reported in either group. These findings might suggest a potential advantage of nab-paclitaxel combined with trastuzumab and pertuzumab compared with the standard regimen in neoadjuvant therapy for patients with HER2-positive early breast cancer, suggesting that this new combination might establish a new standard for neoadjuvant treatment in this patient population. National Natural Science Foundation of China, and Science and Technology Research Projects of Henan Province, China. For the Chinese translation of the abstract see Supplementary Materials section.

Na–Ca co-doping modified g-C 3 N 4 were prepared through the one pot thermal polymerization under a mixture consisting of melamine and sodium chloride-calcium chloride bi-component metal salt in different proportions. The photocatalytic NO X degradation performance of prepared samples were assessed by NO X toxicity. The results showed that the lowest NO X toxicity of co-doping modified g-C 3 N 4 is 3.49 and 1.77 times than that of Na and Ca single-doping modified g-C 3 N 4 when the weight ratio of melamine to metal salt was 1:0.3. X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscope (SEM), N 2 adsorption–desorption were used to characterize the crystalline structures and morphologies of products. Infrared spectrum analyzer (FT-IR), X-ray photoelectron spectroscopy (XPS) were used to study the effects of Na–Ca on the chemical composition of products. And the optical performance of products was characterized by ultraviolet–visible spectra (UV–Vis) and optical luminescence (PL). The results showed that Na–Ca co-doping had a synergic effect on NO X degradation. The larger surface area is equivalent to the increase of photocatalyst dosage. Sodium doping increases NO degradation efficiency by promoting redox capacity and the separation of electron-hole pairs, calcium doping can enhance the chemisorption of NO 2 because of the generation of CaCO 3 and thus reduce the emission of NO 2 .

We study the thermodynamics and the susceptibilities of quark matter in the framework of two-flavor Nambu–Jona–Lasinio model at finite isospin chemical potential and temperature. Isospin number density, normalized energy density and trace anomaly are shown to be in good agreement with the available lattice data as well as with the results from chiral perturbation theory at zero temperature. We also study how susceptibilities depend on the isospin chemical potential and on temperature. We find a peak for the chiral, pion, and isospin susceptibilities at the critical isospin chemical potential, μ I c ( T ) , at the boundary of the phase transition between the normal and pion superfluid phase. Moreover, temperature makes the transition from normal to pion condensed phase smoother. We also note that the pion susceptibility always remains zero in the normal phase while it is finite in the superfluid phase.

Purpose To investigate the optimal cycles of induction chemotherapy (IC) in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Methods We included LANPC patients treated with two or three IC cycles from January 2015 to December 2021. The chi-square test, Kaplan-Meier method, propensity score matching (PSM), and Multivariate Cox regression analyses were used for statistical analysis. Results A total of 491 patients were included in this study, of whom 166 (33.8%) received two cycles and 325 (66.2%) received three cycles of IC. Patients with stage IVA disease ( P  < 0.001), advanced T stage ( P  = 0.011), and advanced N stage ( P  < 0.001) were more likely to receive three cycles of IC. Cox proportional hazards regression analyses showed that the number of IC cycles was not associated with better survival outcomes. Patients who received three cycles of IC had comparable LRFS (HR 0.992, 95% CI 0.525–1.875, P  = 0.981), DMFS (HR 0.805, 95% CI 0.511–1.092, P  = 0.351), PFS (HR 0.917, 95% CI 0.633–1.328, P  = 0.645) and OS (HR 0.880, 95% CI 0.552–1.402, P  = 0.590) compared to those with two cycles of IC. Similar results were found after PSM. No significant differences were found in the incidence of Grade 3–4 acute toxicities between the two and three-cycle groups. However, three cycles of IC significantly increased the incidence of Grade 1–2 leukopenia ( P  = 0.001), neutropenia ( P  = 0.015), anemia ( P  = 0.017), and vomiting ( P  = 0.024) compared to two cycles of IC. Conclusions The number of IC cycles (two or three) did not seem to affect the survival outcome of LANPC patients in this retrospective analysis. However, three cycles of IC were associated with a higher incidence of mild to moderate acute toxicities. Prospective studies in well-defined patient groups with a more uniform treatment program differing only in the number of IC cycles are warranted.