Search

Rui Bai,1,2 Yuhang Sui,1,2 Tianqi Lu,1,2 Hua Chen,1,2 Gang Wang,1,2 Rui Kong,1,2 Hongtao Tan,1,2 Yongwei Wang,1,2 Guanqun Li,1,2 Bei Sun1,2 1Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Guanqun Li; Bei Sun, Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, People’s Republic of China, Email liguanqun@hrbmu.edu.cn; sunbei70@hrbmu.edu.cnPurpose: The effects of the step-jump approach on the survival and prognosis of infected pancreatic necrosis (IPN) patients have not yet been determined.Patients and Methods: Between November 2018 and June 2023, 188 patients were included in this study. There were 144 patients in the step-up group (the SU group) and 44 in the step-jump group (the SJ group). In the SU group, patients successfully treated with percutaneous catheter drainage (PCD) alone were classified into the SU-1 group (n=101), while those requiring additional surgery after PCD were categorized into the SU-2 group (n=43). In the SJ group, patients who underwent minimally invasive necrosectomy (MIN) without PCD were assigned to the SJ-1 group (n=34), whereas those who initially underwent PCD followed by immediate open surgery were placed in the SJ-2 group (n=10). Propensity score matching (PSM) was used to mitigate bias.Results: After PSM, a total of 34 pairs were successfully matched. A comparison of the SU group with the SJ-1 group (upfront MIN without PCD) revealed similar mortality rates (P=0.239); however, the incidences of multiple drug-resistant organisms (MDROs) (P=0.029) and surgical complications (P< 0.001) were significantly lower in the SJ-1 group. After comparing the SU-2 and SJ-2 groups (patients who underwent direct open necrosectomy without MIN after PCD failure), the incidences of surgical complications and MDRO in the SJ-2 group were significantly lower (P< 0.05).Conclusion: Compared with the step-up approach, the step-jump approach is safer and more effective and can significantly reduce the incidence of MDRO and surgical complications.Keywords: infected pancreatic necrosis, step-up approach, step-jump approach, propensity score match

Xinyan Hu,1,&ast; Yanling Sui,1,&ast; Xinhao Yang,1 Zhengyu Yang,2 Qiuting Wang,2 Jiehong Yuan,2 Maoyu Li,1 Xiaotong Ma,1 Chengxuan Qiu,3 Qinjian Sun1 1Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 3Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden&ast;These authors contributed equally to this workCorrespondence: Qinjian Sun, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Neurology, Shandong Provincial Hospital affiliated to Shandong First Medical University, No. 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, People’s Republic of China, Email sqj1210@163.comBackground: The inflammatory response is a pivotal factor in accelerating the progression of atherosclerosis. The high-sensitivity C-reactive protein-to-albumin ratio (CAR) has emerged as a novel marker of systemic inflammation. However, few studies have shown the CAR to be a promising prognostic marker for carotid atherosclerotic disease. This study aimed to analyse the predictive role of the CAR in carotid atherosclerotic disease.Methods: This community-based cohort study recruited 2003 participants from the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) study who were free of stroke or transient ischemic attack. Carotid atherosclerotic plaques and their stability were identified via carotid ultrasound. Logistic regression models were utilized to investigate the association between CAR and the presence of carotid atherosclerotic plaques.Results: The prevalence of carotid atherosclerotic plaques was 38.79% in this study. After adjusting for clinical risk factors, including sex, age, dyslipidemia, hypertension, diabetes mellitus (DM), and smoking and drinking habits, a high CAR-level was independently associated with carotid plaque (odds ratio [OR] of upper: 1.46, 95% confidence interval [CI]: 1.13– 1.90, P = 0.004; P for trend = 0.011). The highest CAR tertile was still significantly associated with carotid plaques among middle-aged (40– 64 years) or female participants. Notably, an elevated CAR may be an independent risk factor for vulnerable carotid plaques (OR of upper: 2.06, 95% CI: 1.42– 2.98, P < 0.001; P for trend < 0.001).Conclusion: A high CAR may be correlated with a high risk of carotid plaques, particularly among mildly aged adults (40– 64 years) or females. Importantly, the CAR may be associated with vulnerable carotid plaques, suggesting that the CAR may be a new indicator for stroke prevention. Keywords: C-reactive protein, albumin, plaque, atherosclerotic, cohort study

OBJECTIVE: The aim of this study was to screen the differential genes related to ferroptosis in osteoporosis patients. MATERIALS AND METHODS: GEO2R was used to screen the differential genes related to ferroptosis in osteoporosis patients by searching the relevant chips in the GEO database, and Spearman's correlation analysis was used to describe the correlation between quantitative variables without normal distribution. p-values lower than 0.05 were considered statistically significant. Another group of osteoporosis patients was selected in the GEO database to verify the significantly differentially expressed genes. RESULTS: The results showed that 10 samples in chip GSE35956 were identified as research objects, and a total of 5 ferroptosis differential genes were screened out: ATP5MC3, CDKN1A, MT1G, NCOA4, SLC1A5, of which 3 up-regulated genes (CDKN1A, MT1G, SLC1A5), 2 down-regulated genes (ATP5MC3, NCOA4). The above differential genes were placed in 19 samples of chip GSE35959 for verification, and the same expression trend was obtained, but only the MT1G difference was statistically significant. CONCLUSIONS: The gene correlation test found that MT1G and ATP5MC3 had a strong negative correlation. [ABSTRACT FROM AUTHOR]

To report a case of popular acantholytic dyskeratosis of the right scrotum. A 58-year-old man complained of pruritic papules on the right scrotum for over 5 years. Dermatologic examination revealed unevenly distributed, millet to green bean sized papules with erosion and maceration, on the right groin. Histopathological changes included hyperkeratosis, parakeratosis, irregular epidermal hyperplasia, acantholysis, intraepidermal vesicles, with a large number of dyskeratotic cells in addition to infiltration of lymphocytes and plasma cells in the dermis. Patient was diagnosed with papular acantholytic dyskeratosis and treated with fractional CO2 laser, and the rashes repeatedly relapsed when followed up 2 years later.

Abstract Advanced light management techniques can enhance the sunlight absorption of perovskite solar cells (PSCs). When located at the front, they may act as a UV barrier, which is paramount for protecting the perovskite layer against UV-enabled degradation. Although it was recently shown that photonic structures such as Escher-like patterns could approach the theoretical Lambertian-limit of light trapping, it remains challenging to also implement UV protection properties for these diffractive structures while maintaining broadband absorption gains. Here, we propose a checkerboard (CB) tile pattern with designated UV photon conversion capability. Through a combined optical and electrical modeling approach, this photonic structure can increase photocurrent and power conversion efficiency in ultrathin PSCs by 25.9% and 28.2%, respectively. We further introduce a luminescent down-shifting encapsulant that converts the UV irradiation into Visible photons matching the solar cell absorption spectrum. To this end, experimentally obtained absorption and emission profiles of state-of-the-art down-shifting materials (i.e., lanthanide-based organic-inorganic hybrids) are used to predict potential gains from harnessing the UV energy. We demonstrate that at least 94% of the impinging UV radiation can be effectively converted into the Visible spectral range. Photonic protection from high-energy photons contributes to the market deployment of perovskite solar cell technology, and may become crucial for Space applications under AM0 illumination. By combining light trapping with luminescent downshifting layers, this work unravels a potential photonic solution to overcome UV degradation in PSCs while circumventing optical losses in ultrathin cells, thus improving both performance and stability.

In order to obtain the influencing rule of secondary combustion on emissions and combustion oscillation characteristics of gas turbine axial staged combustor in non-premixed combustion mode and explore a load increasing mode with stable low emission, an axial staged combustor for F-class gas turbines is selected for experimental study. The results show that CO consumption is restrained and CO emission increases sharply when secondary fuel is added at a lower combustor outlet temperature. The addition of secondary fuel and the increase of secondary equivalence ratio lead to the reduction of NOx emission, but the increase of load can weaken the ability of secondary fuel to reduce NOx emission. The addition of secondary fuel and the increase of secondary equivalence ratio restrain the combustion oscillation in the low frequency band (75—90 Hz). When the secondary equivalence ratio is higher than a certain threshold (0.19), the addition of secondary fuel can restrain higher frequency(175—210 Hz) combustion oscillation. In addition, by comprehensively considering the influence of secondary combustion on emissions and combustion oscillation, the operating range and load increasing mode of low emissions and stable combustion of axial staged combustor in the higher load range (20%—50% load) are obtained, which provides a reference for stable low emission operation of the unit during load increasing.

Objective To investigate the protective effect of dihydromyricetin (DMY) against injury of primary hip-pocampal neurons caused by ferric ammonium citrate (FAC) and its mechanism. Methods Primary hippocampal neurons were collected from 24-hour neonatal Sprague-Dawley rats for in vitro culture, and CCK-8 assay was used to measure the viability of primary hippocampal neurons treated with different concentrations of DMY and determine the administration concentration of DMY. Primary hippocampal neurons were divided into control group (H group), 100 mmol/L DMY treatment group (I group), 250 mmol/L FAC treatment group (J group), and 100 mmol/L DMY+250 mmol/L FAC treatment group (K group). Flow cytometry was used to measure the content of reactive oxygen species (ROS) in each group; colorimetry was used to measure the content of malondialdehyde (MDA) in each group; Western blot was used to measure the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) in each group. Results CCK-8 assay showed the highest viability of primary hippocampal neurons at the concentration of 100 mmol/L for DMY (F=9.95,P

Objective To investigate the effect of Tuina combined with auricular acupoint pressing therapy in the treatment of post-stroke constipation. Methods Totally 100 bedridden patients with post-stroke constipation were randomly divided in the observation group and control group, with 50 cases in each group. All patients received comprehensive treatment and routine nursing interventions, and those in the observation group were given Tuina combined with aricular acupoint pressing therapy. The intervention effect was evaluated and compared between two groups. Results The total effective rate was 94. 00%(47/50) in the observation, which was higher than 66. 00%(33/50) in the control group(P＜0. 05). Conclusion Tuina combined with aricular acupoint pressing therapy is effective to relive the symptoms of constipation in bedridden patients with post-stroke constipation. (目的 探讨便秘推拿联合耳穴压豆治疗中风后恢复期便秘的效果。方法 将100例卧床的中风后恢复期便秘患者随机分为观察组及对照组, 各50例。对照组实施常规护理干预, 观察组在对照组基础上增加便秘推拿联合耳穴压豆。评价两组干预效果。结果 观察组总有效率94. 00%(47/50), 高于对照组的66. 00%(33/50), 差异有统计学意义(P＜0. 05)。结论 对中风后恢复期患者采用便秘推拿配合耳穴压豆, 能进一步缓解便秘症状。)

Abstract Background Attracting and supporting a sustainable long-term care (LTC) workforce has been a persistent social policy challenge across the globe. To better attract and retain a sustainable LTC workforce, it is necessary to adopt a unified concept of worker well-being. Meaning of work is an important psychological resource that buffers the negative impacts of adverse working conditions on workers’ motivation, satisfaction, and turnover intention. The aim of this study was to explore the positive meaning of care work with older people and its implications for health care workers’ job satisfaction and motivation to work in the LTC sector. Methods This study adopted a qualitative descriptive design that pays particular attention to health care workers; such as nurses, personal care workers; as active agents of the meaning making and reframing of care work in LTC communities in a East Asia city. In-depth semi-structured interviews were conducted with thirty health care workers in LTC communities in Hong Kong. Thematic analysis was employed for data analysis. Results The research findings indicate that while health care workers perform demanding care work and experience external constraints, they actively construct positive meanings of care work with older people as a helping career that enables them to facilitate the comfortable aging of older people, build affectional relationships, achieve professional identity, and gain job security. Conclusions This qualitative study explores how health care workers negotiate the positive meaning of older people care work and the implications of meaningful work for workers’ job satisfaction and motivation to work in the LTC sector. The importance of a culturally sensitive perspective in researching and developing social policy intervention are suggested.

With the continuous advancement of agricultural Internet of Things (IoT) technologies, real-time monitoring of agricultural environments has become increasingly significant. This monitoring provides valuable information on pest and disease occurrences and corresponding ecological conditions. However, as the agricultural environments have extensive coverage, the number of monitoring IoT devices and the volume of information will rapidly increase. This leads to a surge in network traffic and computing demands. To address this issue, this article proposes an agricultural environmental monitoring IoT system that utilizes edge computing and deep learning technologies. It combines the Long-Range Wide Area Network (LoRaWAN) for long-range transmission with pest recognition and counting modules. By offloading workloads traditionally processed in the cloud to edge nodes, the proposed system effectively reduces transmission and cloud computing pressures for the agricultural monitoring IoT. Simulation experiments demonstrate stable LoRaWAN protocol-based data transmission at the edge, with an overall packet loss rate of less than 5%, meeting the transmission quality requirements. Moreover, this article investigates a pest recognition and counting method based on deep learning technology. Pest images, captured by monitoring nodes, are recognized and counted online using the TensorFlow framework. Experimental results indicate an accuracy of 89% in pest recognition. By digitally transmitting pest image recognition results to the cloud, the proposed system significantly alleviates transmission and cloud computing pressures for the monitoring IoT.

In order to improve the species composition and structural characteristics of fish in the southern sea area of Zhoushan, the environmental DNA technology was used to detect the fish diversity. By collecting water samples, filtering, extracting environmental DNA, PCR amplification and sequencing, 8 environmental DNA samples were obtained from 6 stations in the southern sea area of Zhoushan, and 9 species of common fish in Zhoushan sea area were detected, including 1 species of cartilaginous fish, 8 species of radial fin fish, and Harpadon nehereus was the dominant species. The results show that, although the environmental DNA technology can not completely replace the traditional methods of fish resources investigation, it can be used as a supplementary means of fish resources investigation and spatial distribution. Combined with bottom trawl data, it provides a basis for the seasonal changes of fish composition and community structure in the southern sea area of Zhoushan.

Aims People who have Alzheimer's disease (AD) often experience sleep disturbances due to the nature of the illness. Melatonin has been prescribed for sleep disturbance in individuals with AD, although there is a lack of national guidelines for pharmacological care for this presentation. Prolonged sleep disturbances for individuals with AD tend to lead to poor quality of life for the individual, behavioural challenges, carers' exhaustion and potential placement breakdowns. The objective of this literature review is to determine whether the available evidence supports recommending melatonin to patients with AD for sleep, along with other benefits and adverse effects. The hypothesis for this review is that melatonin is beneficial for sleep disturbances and has neuroprotection for individuals with AD. Methods Literature search on the online electronic database from 2010 to November 2023, using the title of “Melatonin's effectiveness and the side effects on Alzheimer's Disease''. This literature review was done by screening the 125 searched titles. The inclusion criteria included systematic review (SR), meta-analysis, randomised controlled trial (RCT), animals and cell studies. Exclusion criteria included case studies, literature and peer reviews. A total of 12 papers are included in this review. Results The three SRs, two meta-analyses and one RCT showed the potential effect of melatonin on ameriolating cognitive decline, improving cognition, quality of life and sleep qualities, with the conclusion that further studies are required. One combined meta-analysis and SR showed melatonin might be an effective treatment for mild AD. One Cochrane review showed melatonin has no evidence of improving sleep for moderate-to-severe AD. One animal study and two cellular studies showed a melatonin effect in the control progression of AD. One animal study and one cellular research study concluded that melatonin has potential treatment effects. Adverse effects were mentioned at the higher dose (10mg) with negative reaction times, sedation and confusion. Conclusion There is a potential favourable effect of prescribing melatonin for mild to moderate AD, but there is limited evidence for prescribing it for moderate to severe AD. Furthermore, there is emerging evidence on melatonin's neuroprotective effect and potential treatment options for mild to moderate AD; further research is required for both sleep and neuroprotection in AD.

Solar panels are an environmentally friendly alternative to fossil fuels; however, their useful life is limited to approximately 25 years, after which they become a waste management issue. Proper management and recycling of end-of-life (EOL) solar panels are paramount. It protects the environment because of the high energy consumption of silicon production. We can effectively decrease energy and cost requirements by recovering silicon from recycled solar panels. This is one-third of those needed for manufacturing silicon directly. Moreover, solar panels include heavy metals, such as lead, tin, and cadmium, which pose risks to human health and the environment. Empirical evidence suggests that the costs of mining materials can exceed those of recycled materials, thereby making recycling a more cost-effective means of resource harvesting. This review paper focuses on the techniques developed to delaminate solar panels, which are considered a crucial step in the recycling of EOL solar panels. Initially, various classifications of solar panels are given. Subsequently, an analysis of the diverse methods of solar panel delamination and their efficacy in the retrieval of valued materials is presented. This investigation has identified three primary modes of delamination, namely mechanical, thermal, and chemical. Among these, mechanical delamination is deemed to be a sustainable and cost-effective option when compared to thermal and chemical delamination. The current most popular method of thermal delamination is characterized by its high energy consumption and potential emission, and the chemical delamination generates hazardous liquids that pose their own threat to the environment. This study emphasizes the mechanical delamination techniques, characterized by their environmentally friendly nature, minimal ecological footprint, and capacity to retrieve entire glass panels intact. This paper also discusses the current gaps and potential enhancements for mechanical delamination techniques. For example, some delamination techniques result in crushed materials. Thus, the handling and recovery of materials such as glass and silicon cells require the implementation of an appropriate sorting technique. Also, the value obtained from recovering crushed materials is lower than that of intact glass and silicon cells.

AIM: To investigate the effect of adalimumab combined with dexamethasone intravitreal implant in the treatment of refractory non-infectious uveitis macular edema(UME).METHODS: A total of 92 cases(131 eyes)of refractory non-infectious UME patients admitted to our hospital from January 2020 to January 2022 were selected and randomly divided into control group, with 46 cases(63 eyes)treated with dexamethasone intravitreal implant and observation group, with 46 cases(68 eyes)treated with adalimumab subcutaneous injection combined with dexamethasone intravitreal implant. The best corrected visual acuity(BCVA), central retinal thickness(CRT), vitreous opacity and Th17/Treg cytokines were measured before and after treatment, and the occurrence of adverse reactions was recorded.RESULTS: Totally 3 cases(4 eyes)were lost to follow-up. After treatment for 1, 3, 6 and 12 mo, BCVA was improved in both groups compared with that before treatment, and CRT, vitreous opacity score, serum interleukin(IL)-17 and IL-22 levels were decreased compared with those before treatment, and serum transforming growth factor-β(TGF-β)and IL-10 levels were increased compared with those before treatment. BCVA in the observation group was better than that in the control group, and CRT, vitreous opacity score, serum IL-17 and IL-22 levels were lower than those in the control group, and serum TGF-β and IL-10 levels were higher than those in the control group(all P

BackgroundThe relationship between dissociation and recovery from psychosis is a new topic, which could attract the interest of the researchers in the field of dissociation due to its relevance to their daily clinical practice. This review brings together a diversity of international research and theoretical views on the phenomenology of dissociation, psychosis and recovery and provides a synthesis by narrative and tabulation of the existing knowledge related to these concepts.AimsThe objective was to make a synthesis by narrative and tabulation about what is known on the topic.MethodsThe systematic search was conducted according to the PRISMA-statement in the databases Medline, PsycInfo, PubMed and Google Scholar. 2110 articles were selected according to the inclusion and exclusion criteria detailed in the methods, and 19 records were included in the review.OutcomesNone of the included publications put together, in the same conceptualisation or hypothesis, dissociation and the recovery from an episode of psychosis, therefore this matter remains unstudied at this time.ConclusionThe process of reviewing the existing scientific literature in the field of dissociation and recovery from psychosis has been very useful for charting the direction that future research will take.

Due to the frequent impact of external risks, scientific tourism risk assessment has become the primary task to be implemented in the process of tourism development. Especially with the development of self-driving travel, cross-regional tourism corridors have become an important tourism carrier. However, compared to traditional fixed-location tourism, cross-regional tourism introduces a more intricate landscape of risks. Therefore, there is a pressing need to assess the tourism risks inherent in these corridors. There are many cross-regional tourism corridors in the Tibetan Plateau, but the natural environment of the Tibetan Plateau brings great risks to these tourism corridors. That is why this study focuses on the Tibetan Plateau’s tourism corridors, employing methodologies such as the Analytic Hierarchy Process, entropy weight method, geographic information systems (GIS) spatial analysis, and others to delve into their tourism risk profiles and the influencing factors. Our findings reveal elevated tourism risks across the Tibetan Plateau’s corridors, notably concentrated along the Yunnan–Tibet Line, north Sichuan–Tibet Line, Xinjiang–Tibet Line, Tangfan Ancient Road, Qinghai–Tibet Line, and south Sichuan–Tibet Line. Furthermore, Geodetector was employed to scrutinize the factors influencing tourism risk within the Tibetan Plateau’s corridors, identifying tourism resource endowment, geographical location, precipitation patterns, and economic foundations as primary influencers. Notably, the interaction between these factors exacerbates the overall tourism risk. These insights significantly contribute to the field of tourism risk research and provide a scientific basis for formulating robust tourism safety management strategies within the Tibetan Plateau region.

Purpose: The objective is to evaluate the effectiveness and safety of calcium ionophore as an artificial oocyte activation (AOA) method on pregnancy outcomes in different groups of intracytoplasmic sperm injection (ICSI) patients, providing potential evidence to establish consensus on the indications of AOA., Methods: A systematic comprehensive search was performed in Medline, Embase, the Cochrane Library, and Google Scholar databases. Studies published from January 2014 to June 2024 were searched for analysis. All studies that compared ICSI with AOA-ICSI in routine indications composing impaired fertilization or embryo developmental arrest in previous cycles, or male-factor infertility were included., Results: Twelve studies were included in the meta-analysis. AOA-ICSI was associated with the increase in the overall fertilization rate (OR 1.99, 95% CI 1.16-3.41) and live birth rate (OR 4.58, 95% CI 1.52-13.80). All secondary outcomes including cleavage, blastocyst, high-quality embryo, implantation, biochemical pregnancy, clinical pregnancy presented superiority or equivalence in AOA-ICSI. And the use of calcium ionophore did not increase the miscarriage rate (OR 0.43, 95% CI 0.08-2.43). In subgroup analysis, AOA-ICSI exhibited a more significant effect on patients with indications of no or low fertilization. However, in patients with non-fertilization factors, no statistically significant improvements were observed in all outcomes., Conclusion: Calcium ionophore is an effective artificial oocyte activation approach to improving pregnancy outcomes after ICSI, particularly in cases with indications of fertilization factors, providing further support for the application of AOA in specific populations. Further validation is needed to comprehensively establish the safety of AOA., Trial Registration: PROSPERO registration number CRD42024551481., Competing Interests: Declarations Ethics approval This article is a meta-analysis that no ethical approval is required. Consent of publication This article is a meta-analysis that no consent is required. Standards of Reporting: This systematic review was reported according to the PRISMA 2020 guidelines and PRISMA checklist was fulfilled. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Global microplastic pollution has garnered widespread attention from researchers both domestically and internationally. However, compared to other regions worldwide, little is known about microplastic pollution in the marine ecosystems of the Antarctic region. This study investigated the abundance and characteristics of microplastics (MPs) in the gills and intestines of 15 species of Antarctic fish and Antarctic krill (Euphausia superba). The results indicate that the abundance of MPs in Antarctic fish and E. superba ranged from 0.625 to 2.0 items/individual and 0.17 to 0.27 items/individual, with mean abundances of 0.93 ± 0.96 items/individual and 0.23 ± 0.44 items/individual, respectively. Antarctic fish ingested significantly more MPs than E. superba. There was no significant difference in the abundance of MPs between the gills and intestines of Antarctic fish. However, the quantity of pellet-shaped MPs in the gills was significantly higher than in the intestines. The depth of fish habitat influenced the quantity and size of MPs in their bodies, with benthic fish ingesting significantly fewer MPs than pelagic fish. Pelagic fish ingested significantly more MPs sized 1-5 mm than benthic fish. Additionally, analysis of the characteristics of MPs revealed that fiber-shaped MPs were predominant in shape, with sizes generally smaller than 0.25 mm and 0.25-0.5 mm. The predominant colors of MPs were transparent, red, and black, while the main materials were polypropylene (PP), polystyrene (PS), polyamide (PA), and polyvinyl chloride (PVC). Compared to organisms from other regions, the levels of MPs in Antarctic fish and E. superba were relatively low. This study contributes to a better understanding of the extent of MP pollution in Antarctic fish and E. superba, aiding human efforts to mitigate its impact on the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that may have seemed to impact the research presented in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydrangea-like nickel/nickel-based compounds decorated hollow carbon shells were synthesized through low-temperature calcination and a facile electrochemical oxidation process. This three-dimensional hollow hierarchical structure ensures intimate contact between the electrically conductive nickel (Ni) substrate and uniformly distributed electrochemically active nickel-based compounds. This hierarchical structure offers abundant active sites and accessible pathways, maximizing energy storage, particularly during rapid charge-discharge cycles. With 30 min of electrochemical oxidation, the optimized Ni-compound-based electrode exhibits a specific capacity of 643 C g -1 at 1 A/g. When assembled into a nickel-zinc battery cell with a zinc foil anode, the cell demonstrates swift current responses, with full capacity recovery even after a twentyfold increase in current density, followed by a return to 1 A/g. Density functional theory computations reveal that the electrochemical oxidation, conducted for an optimized duration, results in partial oxidation of Ni(OH) 2 , reducing the surface adsorption energy of OH - from the electrolyte and improving charge storage capacity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: Nonhealing ulcers are difficult to manage because they deviate from the normal wound healing process. Conventional therapy cannot achieve satisfactory therapeutic effects. To verify the effectiveness of combined treatment with human umbilical cord mesenchymal stem cells (hUMSCs) and platelet-rich plasma (PRP) for nonhealing ulcers, we studied a patient with left lower limb venous ulcer (LEVU) treated with combined injection therapy., Patient Concerns: We present the case of a LEVU patient who has not healed for a long period of time (up to 1 year)., Diagnoses: LEVU was diagnosed with clinical symptoms., Interventions: The hUMSCs plus PRP were injected into the wound edge and base (1 µL of cells/cm2 of wound surface), 0.5 mL at each point, with a distance of approximately 1 to 3 cm between points. The injection point was determined according to the extent of wound involvement., Outcomes: Seven days after hUMSC + PRP application, the wound area decreased by nearly 50%. The ulcers had almost completely healed by day 62, and no serious treatment-related toxic side effects were observed., Lessons: hUMSCs can improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. PRP has also been suggested to promote wound healing through the secretion of various nutritional factors. The combination of hUMSCs and PRP has a mutually reinforcing effect, which may achieve a 1 + 1 > 2 effect. Therefore, the combination of hUMSCs and PRP may be a safe and effective treatment option for LEVU., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hypopituitarism, one or more pituitary hormones inefficiently produced by the anterior pituitary or released from the posterior pituitary to adapt to the needs of the organism. Existing epidemiological data show that immune-mediated diffuse infiltration of the anterior pituitary is important in the development of hypopituitarism. However, the precise connection between immune cells and hypopituitarism remains unclear. This study aimed to elucidate the potential causal links between the 731 immune cell types and hypopituitarism risk., Methods: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample Mendelian Randomization (MR) analysis was performed using five methods to explore the potential influence of immune cell phenotypes on hypopituitarism. Sensitivity analyses were conducted to examine the robustness of these findings., Results: Our findings support that B cells, T cells, Tregs, dendritic cells, monocytes, and myeloid cells each have a bidirectional influence on hypopituitarism. One B-cell phenotype was associated with increased hypopituitarism risk, while two B-cell phenotypes play a protective role in hypopituitarism. Moreover, seven T-cell phenotypes demonstrate significant protective properties on hypopituitarism. Seven Tregs were associated with increased hypopituitarism risk. Furthermore, one monocyte was identified to be significantly associated with hypopituitarism risk. In addition, reverse MR analysis revealed that hypopituitarism was positively associated with 30 additional immune cell phenotypes and negatively associated with 17 immune cells., Conclusion: Our investigation shed light on the intricate potential relationship between immune cells and hypopituitarism via genetic methods, underscoring the immune-mediated pathway in hypopituitarism pathogenesis, thereby offering valuable insights for future clinical investigations., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The kidney plays a crucial role in maintaining the body's microenvironment homeostasis. However, current treatment options and therapeutic agents for chronic kidney disease (CKD) are limited. Fortunately, the advent of kidney organoids has introduced a novel in vitro model for studying kidney diseases and drug screening. Despite significant efforts has been leveraged to mimic the spatial-temporal dynamics of fetal renal development in various types of kidney organoids, there is still a discrepancy in cell types and maturity compared to native kidney tissue. The extracellular matrix (ECM) plays a crucial role in regulating cellular signaling, which ultimately affects cell fate decision. As a result, ECM can refine the microenvironment of organoids, promoting their efficient differentiation and maturation. This review examines the existing techniques for culturing kidney organoids, evaluates the strengths and weaknesses of various types of kidney organoids, and assesses the advancements and limitations associated with the utilization of the ECM in kidney organoid culture. Additionally, it presents a discussion on constructing specific physiological and pathological microenvironments using decellularized extracellular matrix during certain developmental stages or disease occurrences, aiding the development of kidney organoids and disease models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Sui, Liu, Xiong, Li, Guo, Xu and Zhang.)

Competing Interests: Conflict of Interest The authors confirm that there are no conflicts of interest.

The molecular mechanisms underlying the neurodevelopmental disorders (NDDs) caused by DDX3X variants remain poorly understood. In this study, we validated that de novo DDX3X variants are enriched in female developmental delay (DD) patients and mainly affect the evolutionarily conserved amino acids based on a meta-analysis of 46,612 NDD trios. We generated a ddx3x deficient zebrafish allele, which exhibited reduced survival rate, DD, microcephaly, adaptation defects, anxiolytic behaviors, social interaction deficits, and impaired spatial recognitive memory. As revealed by single-nucleus RNA sequencing and biological validations, ddx3x deficiency leads to reduced neural stem cell pool, decreased total neuron number, and imbalanced differentiation of excitatory and inhibitory neurons, which are responsible for the behavioral defects. Indeed, the supplementation of L-glutamate or glutamate receptor agonist ly404039 could partly rescue the adaptation and social deficits. Mechanistically, we reveal that the ddx3x deficiency attenuates the stability of the crebbp mRNA, which in turn causes downregulation of Notch signaling and defects in neurogenesis. Our study sheds light on the molecular pathology underlying the abnormal neurodevelopment and behavior of NDD patients with DDX3X mutations, as well as providing potential therapeutic targets for the precision treatment., Competing Interests: Competing interests statement:E.E.E. is a scientific advisory board (SAB) member of Variant Bio, Inc.

Background: The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window., Methods: The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis., Results: A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design., Discussion: Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety., Trial Registration Number: ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147)., Competing Interests: Competing interests: XC reported grant support from the National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality. YS reported honoraria from Boehringer Ingelheim (China) Investment Co. The other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gallbladder cancer (GBC) is a highly aggressive malignancy lacking clinically available targeted therapeutic agents. Super-enhancers (SEs) are crucial epigenetic cis-regulatory elements whose extensive reprogramming drives aberrant transcription in cancers. To study SE in GBC, the genomic distribution of H3K27ac is profiled in multiple GBC tissue and cell line samples to establish the SE landscape and its associated core regulatory circuitry (CRC). The biliary lineage factor SOX9 and Wnt pathway effector TCF7L2, two master transcription factor (TF) candidates identified by CRC analysis, are verified to co-occupy each other's SE region, forming a mutually autoregulatory loop to drive oncogenic SE reprogramming in a subset of GBC. The SOX9/TCF7L2 double-high GBC cells are highly dependent on the two TFs and enriched of SE-associated gene signatures related to stemness, ErbB and Wnt pathways. Patients with more such GBC cells exhibited significantly worse prognosis. Furthermore, SOX9/TCF7L2 double-high GBC preclinical models are found to be susceptible to SE-targeted CDK7 inhibition therapy in vitro and in vivo. Together, this study provides novel insights into the epigenetic mechanisms underlying the oncogenesis of a subset of GBCs with poorer prognosis and illustrates promising prognostic stratification and therapeutic strategies for treating those GBC patients in future clinical trials., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Choline and its derivative betaine are important methyl donors, components of cell membrane phospholipids, or precursors of the neurotransmitter acetylcholine and the gut microbial metabolite trimethylamine-N-oxide. We aimed to investigate trends in dietary intake and food sources of total choline, individual choline forms, and betaine in Chinese adults using data from the China Health and Nutrition Survey (CHNS) 1991-2011. The sample was drawn from urban and rural communities in 12 provinces or autonomous regions with a multistage, random cluster design. Dietary intake was estimated using three consecutive 24-hour dietary recalls in combination with a household food inventory. Linear mixed-effect models were constructed to calculate adjusted mean intake values and 95% confidence intervals (CIs) using R version 4.2.2. A total of 11,188 men and 12,279 women aged 18 years or older were included. Between 1991 and 2011, total choline intake increased from 219.3 (95% CI: 215.1-223.4) mg/d to 269.0 (95% CI: 265.6-272.5) mg/d in men and from 195.6 (95% CI: 191.8-199.4) mg/d to 240.4 (95% CI: 237.4-243.5) mg/d in women (both P -trends <0.001). Phosphatidylcholine was the major form of dietary choline and its contribution to total choline increased from 46.9% in 1991 to 58.8% in 2011. Cereals were the primary food source of total choline before 2000 while eggs had ranked at the top since 2004. Dietary betaine intake was relatively steady over time with a range of 134.0-151.5 mg/d in men ( P -trend <0.001) and 111.7-125.3 mg/d in women ( P -trend >0.05). In conclusion, Chinese adults experienced a significant increase in dietary intake of choline, particularly phosphatidylcholine during 1991-2011 and animal-derived foods have replaced plant-based foods as the main food sources of choline. Betaine intake remained relatively stable over time. Future efforts should address the health effects of these changes.

Introduction: The Alzheimer's Prevention Initiative (API) Generation Studies evaluated the BACE inhibitor umibecestat for Alzheimer's disease (AD) prevention. The studies were terminated early, and the reversibility of umibecestat's side effects was assessed., Methods: Cognitively unimpaired 60- to 75-year-old apolipoprotein E (APOE) ε4 homozygotes and heterozygotes (the latter with elevated brain amyloid deposition) (n = 1556) received umibecestat (50 or 15 mg daily) or placebo for 7 months on average and were followed for a median (interquartile range) of 4 (3 to 6) months after washout., Results: Compared to placebo, umibecestat-treated participants had small, non-progressive, but statistically significant decline in performance on certain cognitive batteries including Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and API Preclinical Composite Cognitive test, but not Clinical Dementia Rating-Sum of Boxes. RBANS differences were no longer significant at the end of follow-up., Discussion: In people at genetic risk for AD, high-dose beta-site amyloid precursor protein cleaving enzyme (BACE) inhibition was associated with early mild cognitive worsening, which reversed shortly after washout, suggesting a symptomatic side effect not associated with neurodegeneration. Fully anonymized data, images, and samples are available upon request for further research on BACE inhibition., Highlights: This is the first trial with blinded assessment of reversibility of BACE inhibitor side effects. Umibecestat was tested in cognitively unimpaired persons at genetic risk for AD. Umibecestat led to early mild cognitive decline that reversed shortly after washout. This suggests a potentially manageable effect not associated with neurodegeneration. Further research may determine the future of BACE inhibition in AD prevention., (© 2024 Novartis Pharma AG. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

JOURNAL/nrgr/04.03/01300535-202419110-00032/figure1/v/2024-03-08T184507Z/r/image-tiff High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases, yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown. Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel (Healaflow®). Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure. Our results identified a total of 12 cell types, namely retinal pigment epithelial cells, rod-photoreceptor cells, bipolar cells, Müller cells, microglia, cone-photoreceptor cells, retinal ganglion cells, endothelial cells, retinal progenitor cells, oligodendrocytes, pericytes, and fibroblasts. The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells, with ganglion cells decreased by 23%. Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure. We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression. We found upregulation of the B3gat2 gene, which is associated with neuronal migration and adhesion, and downregulation of the Tsc22d gene, which participates in inhibition of inflammation. This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure. These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Abstract: Heart failure has always been a prevalent, disabling, and potentially life-threatening disease. For the treatment of heart failure, controlling cardiac remodeling is very important. In recent years, clinical trials have shown that sodium-glucose cotransporter-2 (SGLT-2) inhibitors not only excel in lowering glucose levels but also demonstrate favorable cardiovascular protective effects. However, the precise mechanisms behind the cardiovascular benefits of SGLT-2 inhibitors remain elusive. In this research, we assessed the impact of canagliflozin (CANA, an SGLT-2 inhibitor) on cardiac remodeling progression in mice and preliminarily elucidated the possible mechanism of action of the SGLT-2 inhibitor. Our results indicate that the administration of canagliflozin significantly attenuates myocardial hypertrophy and fibrosis and enhances cardiac ejection function in mice with isoprenaline (ISO)-induced cardiac remodeling. Notably, excessive mitophagy, along with mitochondrial structural abnormalities observed in ISO-induced cardiac remodeling, was mitigated by canagliflozin treatment, thereby attenuating cardiac remodeling progression. Furthermore, the differential expression of AMPK/PINK1/Parkin pathway-related proteins in ISO-induced cardiac remodeling was effectively reversed by canagliflozin, suggesting the therapeutic potential of targeting this pathway with the drug. Thus, our study indicates that canagliflozin holds promise in mitigating cardiac injury, enhancing cardiac function, and potentially exerting cardioprotective effects by modulating mitochondrial function and mitophagy through the AMPK/PINK1/Parkin pathway., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The advancement of rechargeable Mg-metal batteries (RMBs) is severely impeded by the lack of suitable cathode materials. Despite the good cyclic stability of intercalation-type compounds, their specific capacity is relatively low. Conversely, the conversion-type cathodes can deliver a higher capacity but often suffer from poor cycling reversibility and stability. Herein, a WSe 2 /Se intercalation-conversion hybrid material with elemental Se uniformly distributed into WSe 2 nanosheets is fabricated via a simple solvothermal method for high-performance RMBs. The uniformly introduced Se confined in WSe 2 nanosheets can not only efficiently improve the conductivity of the hybrid cathodes, facilitating the fast electron transport and ion diffusion, but also provide additional specific capacity. Besides, the WSe 2 can effectively inhibit the detrimental Se dissolution and polyselenide shuttle, thereby activating the activity of Se and improving its utilization. Consequently, the synergy of intercalation and conversion mechanisms endows WSe 2 /Se hybrids with superior reversible capacity of 252 mAh g -1  at 0.1 A g -1 and ultra-long cyclability of up to 5000 cycles at 2.0 A g -1 with capacity retention of 78.1%. This work demonstrates the feasibility of the strategy by integrating intercalation and conversion mechanisms for developing high-performance cathode materials for RMBs., (© 2024 Wiley‐VCH GmbH.)

Bacterial vaccines play a crucial role in combating bacterial infectious diseases. Apart from the prevention of disease, bacterial vaccines also help to reduce the mortality rates in infected populations. Advancements in vaccine development technologies have addressed the constraints of traditional vaccine design, providing novel approaches for the development of next-generation vaccines. Advancements in reverse vaccinology, bioinformatics, and comparative proteomics have opened horizons in vaccine development. Specifically, the use of protein structural data in crafting multi-epitope vaccines (MEVs) to target pathogens has become an important research focus in vaccinology. In this review, we focused on describing the methodologies and tools for epitope vaccine development, along with recent progress in this field. Moreover, this article also discusses the challenges in epitope vaccine development, providing insights for the future development of bacterial multi-epitope genetically engineered vaccines., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polygenic risk scores (PRS) continue to improve with novel methods and expanding genome-wide association studies. Healthcare and commercial laboratories are increasingly deploying PRS reports to patients, but it is unknown how the classification of high polygenic risk changes across individual PRS. Here, we assessed association and classification performance of cataloged PRS for three complex traits. We chronologically ordered all trait-related publications (Pub n ) and identified the single PRS Best(Pub n ) for each Pub n that had the strongest association with the target outcome. While each Best(Pub n ) demonstrated generally consistent population-level strengths of associations, classification of individuals in the top 10% of each Best(Pub n ) distribution varied widely. Using the PRSmix framework, which integrates information across several PRS to improve prediction, we generate corresponding ChronoAdd(Pub n ) scores for each Pub n that combine all polygenic scores from all publications up to and including Pub n . When compared with Best(Pub n ), ChronoAdd(Pub n ) scores demonstrated more consistent high-risk classification amongst themselves. This integrative scoring approach provides stable and reliable classification of high-risk individuals, and is an adaptable framework into which new scores can be incorporated as they are introduced, integrating easily with current PRS implementation strategies.

Rationale and Objectives: Non-muscle-invasive bladder cancer (NMIBC) is highly recurrent, with each recurrence potentially progressing to muscle-invasive cancer, affecting patient prognosis. Intratumoral heterogeneity plays a crucial role in NMIBC recurrence. This study investigated a novel habitat-based radiomic analysis for stratifying NMIBC recurrence risk., Materials and Methods: A retrospective collection of 382 NMIBC patients between 2015 and 2021 from two medical institutions was carried out. Patients' CT images were collected across three phases, with tumor sites delineated within the bladder. Intratumoral habitats were identified using K-means clustering on 19 texture features of the tumor sites, followed by the extraction of 107 radiomic features per habitat with PyRadiomics. These features were integrated into machine learning algorithms to develop a habitat-based model (HBM) for predicting two-year recurrence of NMIBC patients. The clinical and multiphase radiomic models were also constructed for comparison, with the Delong test comparing their diagnostic efficiency. The impact of HMB on patients' recurrence-free survival and the correlation between HBM and tumor-stroma ratio were further analyzed., Results: Three distinct habitats were identified within NMIBC. The HBM showed an AUC of 0.932 (95% CI: 0.906 - 0.958) in the training cohort and 0.782 (95% CI: 0.674 - 0.890) in the validation cohort for predicting two-year recurrence. With comparison between different models, The HBM is demonstrated to possess superior diagnostic efficacy to the clinical model (p < 0.001) in the training cohort. However, no significant difference was noted between the multiphase and clinical models (p = 0.130) in the training cohort. The HBM score effectively distinguished the recurrence-free survival of NIMBC patients and demonstrated a significant correlation with the tumor-stroma ratio., Conclusions: Habitat-based radiomics, coupled with machine learning, efficiently predicts NMIBC recurrence. Further research on habitat-based radiomics offers potential improvement in clinical management of NMIBC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest in this manuscript and approve the final version of the submitted manuscript., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIV mac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17 + NKp44 + innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44 + ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ + NKG2A - NKp44 - ILCs, and increased levels of mucosal activated Ki67 + CD4 + T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44 + ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)