The Impacts of Chlorine and Disinfection Byproducts on Antibiotic-Resistant Bacteria (ARB) and Their Conjugative Transfer

Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are emerging contaminants leading to severe worldwide health problems. Chlorination, a widely used procedure, was extensively explored as one of the main methods to remove ARB and ARGs in recent years. In this study, to enrich the analyses of chlorination, several comprehensive effects of the chlorine disinfection system on ARB and their conjugative transfer ability were explored. The results presented that the low dose of chlorine (3-log inactivation rate) triggered cell membrane changes, with little influence on the bacteria in terms of their antibiotic resistance. However, their capacity for conjugative transfer sharply decreased. Minor consumption of chloramphenicol was achieved with the chlorine dose applied in the disinfection system. Monochloroacetonitrile (MCAN) had limited effects on the frequency of conjugative transfer, indicating that the existence of MCAN would not aggravate the dissemination of ARGs by conjugative transfer. The overall impacts of the chlorine disinfection system with different containments on antibiotic resistance need further investigation

Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors

Immunotherapy has revolutionized the established therapeutics against tumors. As the major immunotherapy approach, immune checkpoint inhibitors (ICIs) achieved remarkable success in the treatment of malignancies. However, the clinical gains are far from universal and durable, because of the primary and secondary resistance of tumors to the therapy, or side effects induced by ICIs. There is an urgent need to find safe combinatorial strategies that enhance the response of ICIs for tumor treatment. Diets have an excellent safety profile and have been shown to play pleiotropic roles in tumor prevention, growth, invasion, and metastasis. Accumulating evidence suggests that dietary regimens bolster not only the tolerability but also the efficacy of tumor immunotherapy. In this review, we discussed the mechanisms by which tumor cells evade immune surveillance, focusing on describing the intrinsic and extrinsic mechanisms of resistance to ICIs. We also summarized the impacts of different diets and/or nutrients on the response to ICIs therapy. Combinatory treatments of ICIs therapy with optimized diet regimens own great potential to enhance the efficacy and durable response of ICIs against tumors, which should be routinely considered in clinical settings

Development of a baseline model for MAX/MXene synthesis recipes extraction via pre-trained model with domain knowledge

Due to their unique combination of metallic- and ceramic-like properties, MAX phases have attracted a lot of attentions. By selectively etching A-site atoms, MXenes with unique two-dimensional structures can be potentially generated. Due to their extraordinary properties, MXenes have currently made their way to the forefront of various research areas including electronics, photonics and catalysis. Therefore, the development of novel synthesis strategies for MAX/MXene is a key issue for the further development of MAX/MXene. Distilling insights from scientific literatures could accelerate the exploration of novel synthesis recipes; however, manually extracting scattered information from thousands of journal articles is laborious. In this study, we present an annotated corpus incorporating domain knowledge about MAX/MXene synthesis processes, deriving from experimental sections within 110 papers on MAX/MXene research; and based on that, a baseline model (including named entity recognition (NER) and relation extraction (RE) parts) is proposed for distilling information about MAX/MXene synthesis conditions from literatures using pre-trained natural language processing (NLP) models. We also demonstrate the efficacy of the proposed pipeline owning to the joint effort of domain knowledge (about MAX/MXene) and machine learning; where the entity recognition model possessing optimized setting could detect the entities with F1 score of 0.8452, and for relation extraction model with F1 score of 0.8476. It is hoped that the current work would provide an auxiliary for the future research and development of novel MAX/MXenes. In addition, the developed model could serve as a pre-trained model of MAX/MXenes synthesis routes extraction for future data augment

Potential Allelopathic Interference of <i>Abutilon theophrasti</i> Medik. Powder/Extract on Seed Germination, Seedling Growth and Root System Activity of Maize, Wheat and Soybean

The velvetleaf (Abutilon theophrasti Medik.) is a strong and competitive weed in fields that inhibits the growth of crops. Reports have suggested that allelopathy is one of the reasons for this inhibition; however, the mechanism of this allelopathy remains unclear. In this study, velvetleaf powder/extracts were shown to inhibit seed germination, growth and yield in maize, wheat and soybean through petri dish, pot and field control experiments. We observed a concentration-dependent inhibition of the seed germination rate for all three crops. The root tip structure changed significantly and the embryo even died when irrigated with a high concentration of the extract (10 mg·mL−1). After adding velvetleaf powder, the malondialdehyde (MDA) content in crop seedlings was dose-dependent, and the superoxide dismutase (SOD) activity of maize, wheat and soybean showed the maximum values under treatment with 1.25, 5 and 5 mg·cm−3, respectively. The activity of peroxidase (POD) showed the highest value under the 5 mg·cm−3 treatment in maize and wheat seedlings and under 10 mg·cm−3 treatment in soybean seedlings. However, sugar, protein content and root activity in all three crops was the lowest under the 10 mg·cm−3 treatment. Therefore, velvetleaf may decrease the productivity of three crops by changing the antioxidant enzyme activities, root system activities and root tip structures

Potential Allelopathic Interference of Abutilon theophrasti Medik. Powder/Extract on Seed Germination, Seedling Growth and Root System Activity of Maize, Wheat and Soybean

The velvetleaf (Abutilon theophrasti Medik.) is a strong and competitive weed in fields that inhibits the growth of crops. Reports have suggested that allelopathy is one of the reasons for this inhibition; however, the mechanism of this allelopathy remains unclear. In this study, velvetleaf powder/extracts were shown to inhibit seed germination, growth and yield in maize, wheat and soybean through petri dish, pot and field control experiments. We observed a concentration-dependent inhibition of the seed germination rate for all three crops. The root tip structure changed significantly and the embryo even died when irrigated with a high concentration of the extract (10 mg&middot;mL&minus;1). After adding velvetleaf powder, the malondialdehyde (MDA) content in crop seedlings was dose-dependent, and the superoxide dismutase (SOD) activity of maize, wheat and soybean showed the maximum values under treatment with 1.25, 5 and 5 mg&middot;cm&minus;3, respectively. The activity of peroxidase (POD) showed the highest value under the 5 mg&middot;cm&minus;3 treatment in maize and wheat seedlings and under 10 mg&middot;cm&minus;3 treatment in soybean seedlings. However, sugar, protein content and root activity in all three crops was the lowest under the 10 mg&middot;cm&minus;3 treatment. Therefore, velvetleaf may decrease the productivity of three crops by changing the antioxidant enzyme activities, root system activities and root tip structures

Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer

Abstract The prognosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) remained unsatisfactory currently, more anti-HER2 agents are needed. Here we report a phase I study that evaluated the safety, activity, and biomarkers of LZM005, a HER2 antibody, used as a monotherapy or in combination with trastuzumab plus docetaxel in patients with HER2-positive MBC. From October 2017 to December 2019, 34 patients received LZM005 (14 monotherapy, 20 combination therapy). No DLT was observed. The common adverse events (AEs) in phase Ia included diarrhea (21.4%), infusion reaction (21.4%), and hypertriglyceridemia (21.4%), while those in phase Ib were leukopenia (85.0%), neutropenia (75.0%), anemia (60.0%), diarrhea (60.0%), and rash/pruritus (50.0%). All AEs were manageable. In phase Ia, partial response (PR) was achieved in one case (1/14, overall response rate [ORR]: 7.1%); the disease control rate was 42.90% (6/14). In phase Ib, 11 patients (55.0%) achieved PR, and eight (40.0%) had stable disease. The ORR was 100% (6/6) in trastuzumab-naive and 35.7% (5/14) in trastuzumab-pretreated patients. Biomarker analysis showed that chromatin remodeling genes KMT2B and BRWD1 were associated with better progression-free survival. LZM005 is well tolerated and shows potent activity in patients with HER2-positive MBC

Atomic cerium modulated palladium nanoclusters exsolved ferrite catalysts for lean methane conversion

Abstract The active and stable palladium (Pd) based catalysts for CH4 conversion are of great environmental and industrial significance. Herein, we employed N2 as an optimal activation agent to develop a Pd nanocluster exsolved Ce‐incorporated perovskite ferrite catalyst toward lean methane oxidation. Replacing the traditional initiator of H2, the N2 was found as an effective driving force to selectively touch off the surface exsolution of Pd nanocluster from perovskite framework without deteriorating the overall material robustness. The catalyst showed an outstanding T50 (temperature of 50% conversion) plummeting down to 350°C, outperforming the pristine and H2‐activated counterparts. Further, the combined theoretical and experimental results also deciphered the crucial role that the atomically dispersed Ce ions played in both construction of active sites and CH4 conversion. The isolated Ce located at the A‐site of perovskite framework facilitated the thermodynamic and kinetics of the Pd exsolution process, lowering its formation temperature and promoting its quantity. Moreover, the incorporation of Ce lowered the energy barrier for cleavage of C─H bond, and was dedicated to the preservation of highly reactive PdOx moieties during stability measurement. This work successfully ventures uncharted territory of in situ exsolution to provide a new design thinking for a highly performed catalytic interface

What is the appropriate genetic testing criteria for breast cancer in the Chinese population?—Analysis of genetic and clinical features from a single cancer center database

Abstract Background Genetic testing plays an important role in guiding screening, diagnosis, and precision treatment of breast cancer (BC). However, the appropriate genetic testing criteria remain controversial. The current study aims to facilitate the development of suitable strategies by analyzing the germline mutational profiles and clinicopathological features of large‐scale Chinese BC patients. Methods BC patients who had undergone genetic testing at the Sun Yat‐sen University Cancer Center (SYSUCC) from September 2014 to March 2022 were retrospectively reviewed. Different screening criteria were applied and compared in the population cohort. Results A total of 1035 BC patients were enrolled, 237 pathogenic or likely pathogenic variants (P/LPV) were identified in 235 patients, including 41 out of 203 (19.6%) patients tested only for BRCA1/2 genes, and 194 out of 832 (23.3%) received 21 genes panel testing. Among the 235 P/LPV carriers, 222 (94.5%) met the NCCN high‐risk criteria, and 13 (5.5%) did not. While using Desai's criteria of testing, all females diagnosed with BC by 60 years and NCCN criteria for older patients, 234 (99.6%) met the high‐risk standard, and only one did not. The 21 genes panel testing identified 4.9% of non‐BRCA P/LPVs and a significantly high rate of variants of uncertain significance (VUSs) (33.9%). The most common non‐BRCA P/LPVs were PALB2 (11, 1.3%), TP53 (10, 1.2%), PTEN (3, 0.4%), CHEK2 (3, 0.4%), ATM (3, 0.4%), BARD1 (3, 0.4%), and RAD51C (2, 0.2%). Compared with BRCA1/2 P/LPVs, non‐BRCA P/LPVs showed a significantly low incidence of NCCN criteria listed family history, second primary cancer, and different molecular subtypes. Conclusions Desai's criteria might be a more appropriate genetic testing strategy for Chinese BC patients. Panel testing could identify more non‐BRCA P/LPVs than BRCA1/2 testing alone. Compared with BRCA1/2 P/LPVs, non‐BRCA P/LPVs exhibited different personal and family histories of cancer and molecular subtype distributions. The optimal genetic testing strategy for BC still needs to be investigated with larger continuous population studies