Novel insights into intrinsic mechanisms of magnetic field on long-term performance of anaerobic ammonium oxidation process.

The performance of an anaerobic ammonium oxidation (anammox) reactor with the magnetic field of 40 mT was systematically investigated. The total nitrogen removal rate was enhanced by 16% compared with that of the control group. The enhancing mechanism was elucidated from the improved mass transfer efficiency, the complicated symbiotic interspecific relationship and the improved levels of functional genes. The magnetic field promoted formation of the loose anammox granular sludge and the homogeneous and well-connected porous structure to enhance the mass transfer. Consequently, Candidatus Brocadia predominated in the sludge with an increase in abundance of 13%. Network analysis showed that the positive interactions between Candidatus Brocadia and heterotrophic bacteria were strengthened, which established a more complicated stable microbial community. Moreover, the magnetic field increased the levels of hdh by 26% and hzs by 35% to promote the nitrogen metabolic process. These results provided novel insights into the magnetic field-enhanced anammox process.

Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle-mRNA formulation.

Current treatment options for diabetic wounds face challenges due to low efficacy, as well as potential side effects and the necessity for repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid nanoparticle (TS LNP)-mRNA therapy to accelerate diabetic wound healing by repairing and reprogramming the microenvironment of the wounds. A library of reactive oxygen species (ROS)-responsive TS LNPs was designed and developed to encapsulate interleukin-4 (IL4) mRNA. TS2-IL4 LNP-mRNA effectively scavenges excess ROS at the wound site and induces the expression of IL4 in macrophages, promoting the polarization from the proinflammatory M1 to the anti-inflammatory M2 phenotype at the wound site. In a diabetic wound model of db/db mice, treatment with this formulation significantly accelerates wound healing by enhancing the formation of an intact epidermis, angiogenesis, and myofibroblasts. Overall, this TS LNP-mRNA platform not only provides a safe, effective, and convenient therapeutic strategy for diabetic wound healing but also holds great potential for clinical translation in both acute and chronic wound care.

Adaptive enhancement design of non-significant regions of a Wushu action 3D image based on the symmetric difference algorithm.

The recognition of martial arts movements with the aid of computers has become crucial because of the vigorous promotion of martial arts education in schools in China to support the national essence and the inclusion of martial arts as a physical education test item in the secondary school examination in Shanghai. In this paper, the fundamentals of background difference algorithms are examined and a systematic analysis of the benefits and drawbacks of various background difference algorithms is presented. Background difference algorithm solutions are proposed for a number of common, challenging problems. The empty background is then automatically extracted using a symmetric disparity approach that is proposed for the initialization of background disparity in three-dimensional (3D) photos of martial arts action. It is possible to swiftly remove and manipulate the background, even in intricate martial arts action recognition scenarios. According to the experimental findings, the algorithm's optimized model significantly enhances the foreground segmentation effect of the backdrop disparity in 3D photos of martial arts action. The use of features such as texture probability is coupled to considerably enhance the shadow elimination effect for the shadow problem of background differences.

Analysis of patient-reported outcomes in the approval of novel oncology drugs in the United States, 2017-2022.

Background: With the growing notion of patient-focused drug development, the quality of life and other patient-reported outcomes (PROs) of cancer patients are gaining considerable attention. Several drug regulatory agencies, including the U.S. Food and Drug Administration (FDA), are calling attention to PROs. This review aims to comprehensively characterise the application of PROs and regulatory considerations for PROs in the FDA-approved novel oncology drugs. Methods: The FDA review documents and labels for novel oncology drugs approved from July 2017 to July 2022 were retrieved. We collected and analysed drug approval information, types of endpoints for PROs, PRO measures, designs of trials including PROs, and regulatory comments on PRO-related contents. Findings: Results demonstrated that PROs were used more commonly for solid tumours than hematologic malignancies, which might be correlated with the disease characteristics. We further categorised and analysed existing PRO measures, providing insight for tool selection in future oncology trial design. Our findings also indicated that PROs currently do not play a significant role in oncology drug approvals. The major deficiencies related to PROs commented on by FDA reviewers were analysed, followed by recommendations for improvements. Interpretation: This review demonstrates that PROs currently do not play a significant role in oncology drug marketing review, and how they can be used to support the approval of new oncology drugs is still in the exploratory stage. This current situation is not only related to the deficiencies in the design and implementation of PRO-related contents in oncology trials, but more importantly, it is a reminder that we should pay more attention to patient experience in the development of oncology drugs. Funding: This study was not supported by any funding.

Serologic response and safety of COVID-19 vaccination in HSCT or CAR T-cell recipients: a systematic review and meta-analysis.

BACKGROUND: Patients receiving hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR T-cell) therapy are immunocompromised and at high risk of viral infection, including SAR2-CoV-2 infection. However, the effectiveness and safety of COVID-19 vaccines in these recipients is not well characterized. The present meta-analysis evaluated the serologic response and safety of COVID-19 vaccines in these population. METHODS: Literature databases (MEDLINE, EMBASE, Web of Science, MedRvix and BioRvix) were searched for original studies with serologic response post COVID-19 vaccination in HSCT or CAR T-cell recipients published until July 14, 2022. The analysis included 27 observational studies with a total of 2899 patients receiving allogeneic HSCT (2506), autologous HSCT (286) or CAR T-cell therapy (107), and 683 healthy participants with serologic response data. Random effects models were used to pool the rate of serologic response to COVID-19 vaccination in HSCT or CAR T-cell recipients and odds ratio comparing with healthy controls. RESULTS: The pooled seropositivity rates in HSCT and CAR T-cell recipients were 0.624 [0.506-0.729] for one dose, 0.745 [0.712-0.776] for two doses. The rates were significantly lower than those in healthy controls (nearly 100%). In subgroup analysis, CAR T-cell recipients exhibited an even lower seroconversion rate (one dose: 0.204 [0.094-0.386]; two doses: 0.277 [0.190-0.386]) than HSCT counterparts (one dose: 0.779 [0.666-0.862]; two doses: 0.793 [0.762-0.821]). The rates were comparable between autologous and allogeneic HSCT recipients. Other possible impact factors related to seropositivity were time interval between therapy and vaccination, use of immunosuppressive drugs and immune cell counts. Most vaccine-related adverse effects were mild and resolvable, comparable to general population. CONCLUSIONS: This analysis revealed a diminished response to COVID-19 vaccines in HSCT or CAR T-cell recipients. Our findings may inform regular COVID-19 vaccination at appropriate intervals after HSCT or CAR T-cell therapy.

Identification of Immune-Related Breast Cancer Chemotherapy Resistance Genes via Bioinformatics Approaches.

Chemotherapy resistance in breast cancer is an important factor affecting the prognosis of breast cancer patients. We computationally analyzed the differences in gene expression before and after chemotherapy in breast cancer patients, drug-sensitive groups, and drug-resistant groups. Through functional enrichment analysis, immune microenvironment analysis, and other computational analysis methods, we identified PRC1, GGTLC1, and IRS1 as genes that may mediate breast cancer chemoresistance through the immune pathway. After validation of certain other clinical datasets and in vitro cellular assays, we found that the above three genes influenced drug resistance in breast cancer patients and were closely related to the tumor immune microenvironment. Our finding that chemoresistance in breast cancer could be influenced by the mediation of tumor immunity expanded our knowledge of how to address this problem and could guide future research involving chemoresistance.

Effects of high-flow nasal oxygen cannula versus other noninvasive ventilation in extubated patients: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: A systematic review and meta-analysis were performed to compare the effects of high-flow nasal oxygen cannula (HFNC) and noninvasive ventilation (NIV) in extubated patients with respiratory insufficiency. METHODS: The Cochrane Library, PubMed, and ClinicalTrials.gov were searched from inception to 28 February 2021, to identify randomized controlled trials. The primary outcome was reintubation within 24-72 hours after a planned extubation. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Six articles with1746 patients were included. The effect of HFNC on the reintubation rate was noninferior to that of NIV (OR = 1.11, 95% CI: 0.85-1.44). The rate of treatment failure was 20.40% with HFNC versus 20.92% with NIV; this difference was nonsignificant (OR = 0.97, 95% CI: 0.72-1.32, P = 0.85). HFNC reduced the rates of skin lesion occurrence (10.28% versus 23.82%, OR = 0.37, 95% CI: 0.26-0.53, P < 0.00001) and post-extubation respiratory failure (23.76% versus 25.56%, OR = 0.64, 95% CI: 0.46-0.88, P = 0.006), compared with NIV. CONCLUSIONS: In extubated patients, HFNC was noninferior to NIV in the rate of reintubation and treatment failure. Compared with NIV, HFNC decreased the occurrence of skin lesions and post-extubation respiratory failure.

Early intestinal microbiota changes in aged and adult mice with sepsis.

Background: The mortality rate associated with sepsis in elderly individuals is higher than that in younger individuals. The intestinal microbiota has been demonstrated to play an important role in the occurrence and development of sepsis. The purpose of this study was to investigate the differences in the intestinal microbiota between aged and adult mice with sepsis. Methods: Thirty male C57BL mice were randomly divided into two groups: 15 in the adult group (AD group) and 15 in the age group (Age group). All the mice underwent caecal ligation and puncture to induce sepsis. Mice faeces were collected, and analysed using 16S rRNA sequencing. The liver and colon tissues were collected. Results: There were significant differences in intestinal microbiota composition between the two groups. Compared with adult sepsis mice, the diversity of intestinal microbiota in the aged group was significantly reduced and the structure of dominant intestinal microbiota was changed. In the Age group, the microbiota associated with inflammatory factors increased, and the microbiota associated with the production of SCFAs (Ruminiclostridium, Prevotellaceae_UCG-001, Rikenella, Parabacteroides, Oscillibacter, Odoribacter, Muribaculum, Lachnoclostridium, Intestinimonas, Faecalibaculum, Anaerotruncus, Alloprevotella and Absiella) decreased. The metabolic pathways related to the microbiota also changed. Moreover, the proportion of inflammatory factors in Age group was higher than that in AD group. Conclusion: Our results showed that there were significant differences in the abundance and structure of microbiota between aged and adult sepsis mice, Aged sepsis mice have more severe intestinal microbiota destruction and liver tissue inflammation than adult sepsis mice.

Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of the Malaria Parasite Life Cycle.

Artemisin combination therapy (ACT) is the main treatment option for malaria, which is caused by the intracellular parasite Plasmodium. However, increased resistance to ACT highlights the importance of finding new drugs. Recently, the aspartic proteases Plasmepsin IX and X (PMIX and PMX) were identified as promising drug targets. In this study, we describe dual inhibitors of PMIX and PMX, including WM382, that block multiple stages of the Plasmodium life cycle. We demonstrate that PMX is a master modulator of merozoite invasion and direct maturation of proteins required for invasion, parasite development, and egress. Oral administration of WM382 cured mice of P. berghei and prevented blood infection from the liver. In addition, WM382 was efficacious against P. falciparum asexual infection in humanized mice and prevented transmission to mosquitoes. Selection of resistant P. falciparum in vitro was not achievable. Together, these show that dual PMIX and PMX inhibitors are promising candidates for malaria treatment and prevention.

Evaluation of 4-Amino 2-Anilinoquinazolines against Plasmodium and Other Apicomplexan Parasites In Vitro and in a P. falciparum Humanized NOD-scid IL2Rγnull Mouse Model of Malaria.

A series of 4-amino 2-anilinoquinazolines optimized for activity against the most lethal malaria parasite of humans, Plasmodium falciparum, was evaluated for activity against other human Plasmodium parasites and related apicomplexans that infect humans and animals. Four of the most promising compounds from the 4-amino 2-anilinoquinazoline series were equally as effective against the asexual blood stages of the zoonotic P. knowlesi, suggesting that they could also be effective against the closely related P. vivax, another important human pathogen. The 2-anilinoquinazoline compounds were also potent against an array of P. falciparum parasites resistant to clinically available antimalarial compounds, although slightly less so than against the drug-sensitive 3D7 parasite line. The apicomplexan parasites Toxoplasma gondii, Babesia bovis, and Cryptosporidium parvum were less sensitive to the 2-anilinoquinazoline series with a 50% effective concentration generally in the low micromolar range, suggesting that the yet to be discovered target of these compounds is absent or highly divergent in non-Plasmodium parasites. The 2-anilinoquinazoline compounds act as rapidly as chloroquine in vitro and when tested in rodents displayed a half-life that contributed to the compound's capacity to clear P. falciparum blood stages in a humanized mouse model. At a dose of 50 mg/kg of body weight, adverse effects to the humanized mice were noted, and evaluation against a panel of experimental high-risk off targets indicated some potential off-target activity. Further optimization of the 2-anilinoquinazoline antimalarial class will concentrate on improving in vivo efficacy and addressing adverse risk.