Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors.

BACKGROUND: As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy. METHODS: The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature. RESULTS: The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs' marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer. CONCLUSIONS: The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.

Triphenylamine-Based N,O-Bidentate BF2 -Enolimine Initiator for Three-Arm Star Polymethacrylates with Dual-State Fluorescent Emission.

Three-arm star polymethacrylates with dual-phase (solution and solid-state) fluorescent emission have been synthesized via atom transfer radical polymerization (ATRP) using a triphenylamine-derived organboron complex (TAPA-BKI-3Br) as initiator. The as-synthesized three-arm star polymethacrylates exhibited bright emission in both solution and the solid states due to the highly twisted structure and intramolecular charge transfer (ICT) effect of TAPA-BKI core, as well as the steric effect and restriction of intramolecular motions from the polymer arms. And the polymer chains have an important influence on the photophysical behavior of the as-synthesized three-arm star polymethacrylates in the aggregated state.

Efficacy and safety of oral sodium sulfate tablet compared with 1-L polyethylene glycol plus ascorbate: a prospective, randomized, endoscopist-blinded trial.

BACKGROUND AND AIM: Low-volume bowel preparation solutions, including 1-L polyethylene glycol plus ascorbate (PEG-A), have been developed to improve tolerability. The oral sodium sulfate tablet (OST) is a new agent with simethicone as a preloaded component. We investigated the efficacy, safety, and tolerability of OST compared to 1-L PEG-A. METHODS: A single-center, prospective, controlled study was performed with randomization into the OST (group A) and 1-L PEG-A (group B) groups. Bowel preparation efficacy was assessed on the Boston Bowel Preparation Scale (BBPS) and Bubble Scale. Safety and tolerability were evaluated using a questionnaire and laboratory examination. RESULTS: Final analysis was performed on 171 patients (group A: 87, group B: 84). The proportion of bowel preparation success (BBPS ≥ 2 for each colonic segment) in group A was not inferior compared to group B (95.4% vs 96.4%, P = 0.736, 1-sided 97.5% lower confidence limit -7.0%). The adenoma detection rate was not different (59.6% vs 41.9%; P = 0.087). The bubble scale was better in group A (0.2 ± 0.9 vs 1.9 ± 1.7, P < 0.001). All adverse events were mild in both groups. Nausea was less frequent in group A (14.9% vs 38.1%, P = 0.001). Overall satisfaction was better in group A (8.1 ± 2.1 vs 6.4 ± 2.8, P < 0.001). No clinically significant laboratory abnormality developed in both groups. These findings were similarly shown in old patients ≥65 years. CONCLUSIONS: Both OST and 1-L PEG-A were efficacious, safe, and tolerable for bowel preparation of colonoscopy. The OST showed fewer bubbles and slightly better tolerability.

Astrocytic FoxO1 in the hypothalamus regulates metabolic homeostasis by coordinating neuropeptide Y neuron activity.

The forkhead box transcription factor O1 (FoxO1) is expressed ubiquitously throughout the central nervous system, including in astrocytes, the most prevalent glial cell type in the brain. While the role of FoxO1 in hypothalamic neurons in controlling food intake and energy balance is well-established, the contribution of astrocytic FoxO1 in regulating energy homeostasis has not yet been determined. In the current study, we demonstrate the essential role of hypothalamic astrocytic FoxO1 in maintaining normal neuronal activity in the hypothalamus and whole-body glucose metabolism. Inhibition of FoxO1 function in hypothalamic astrocytes shifts the cellular metabolism from glycolysis to oxidative phosphorylation, enhancing astrocyte ATP production and release meanwhile decreasing astrocytic export of lactate. As a result, specific deletion of astrocytic FoxO1, particularly in the hypothalamus, causes a hyperactivation of hypothalamic neuropeptide Y neurons, which leads to an increase in acute feeding and impaired glucose regulation and ultimately results in diet-induced obesity and systemic glucose dyshomeostasis.

Observer-Based Adaptive NN Security Control for Switched Nonlinear Systems Against DoS Attacks: An ADT Approach.

In this article, a novel switched observer-based neural network (NN) adaptive control algorithm is established, which addresses the security control problem of switched nonlinear systems (SNSs) under denial-of-service (DoS) attacks. The considered SNSs are described in lower triangular form with external disturbances and unmodeled dynamics. Note that when an attack is launched in the sensor-controller channel, the controller will not receive any message, which makes the standard backstepping controller not workable. To tackle the challenge, a set of NN adaptive observers are designed under two different situations, which can switch adaptively depending on the DoS attack on/off. Further, an NN adaptive controller is constructed and the dynamic surface control method is borrowed to surmount the complexity explosion phenomenon. To eliminate double damage from DoS attacks and switches, a set of switching laws with average dwell time are designed via the multiple Lyapunov function method, which in combination with the proposed controllers, guarantees that all the signals in the closed-loop system are bounded. Finally, an illustrative example is offered to verify the availability of the proposed control algorithm.

Long-term impact of angiotensin receptor-neprilysin inhibitor based on short-term treatment response in heart failure.

AIMS: The long-term effect of angiotensin receptor-neprilysin inhibitor (ARNI) remains uncertain in patients who have experienced improvements in left ventricular (LV) systolic function or significant LV reverse remodelling following a certain period of treatment. It is also unclear how ARNI performs in patients who have not shown these improvements. This study aimed to assess the impact of prolonged ARNI use compared with angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) in patients with and without significant treatment response after 1 year of heart failure (HF) treatment. METHODS AND RESULTS: The present study enrolled patients with HF with reduced ejection fraction (HFrEF) who were treated with either ARNI or ACEIs/ARBs within 1 year of undergoing index echocardiography. After 1 year of treatment, patients were reclassified into the following groups: (i) patients with HF with improved ejection fraction and persistent HFrEF and (ii) patients with and without LV reverse remodelling based on the follow-up echocardiography. The effect of ARNI versus that of ACEIs/ARBs in each group was assessed from the time of categorizing into new groups using the composite event of all-cause mortality and HF hospitalization. A total of 671 patients with HFrEF (age, 66.4 ± 14.1 years; males, 66.8%) were included, and 133 (19.8%) composite events of death and rehospitalization for HF were observed during the follow-up (median follow-up, 44 [interquartile range, 34-51] months). ARNI had a significantly lower event rate than ACEIs/ARBs in patients with HF with improved ejection fraction (7.0% vs. 30.4%, P = 0.020) and those with persistent HFrEF (17.6% vs. 49.7%, P < 0.001). Irrespective of whether patients exhibited LV reverse remodelling (15.8% vs. 31.1%, P = 0.001) or not (15.0% vs. 54.9%, P < 0.001), ARNIs were associated with a significantly lower event rate than ACEIs/ARBs. CONCLUSIONS: Regardless of significant treatment response measured by either LVEF or LV reverse remodelling after 1 year of treatment, the extended utilization of ARNI demonstrated a more favourable prognosis than that of ACEIs/ARBs in patients with HFrEF.

Wavefront-splitting interferometer based on orbital angular momentum beams.

Orbital angular momentum (OAM) interferometers have attracted great attention in metrology. However, OAM interferometers usually have large sizes and are difficult to align. OAM-based wavefront-splitting interferometer (WSI-OAM) can achieve nano-displacement measurement with compact size and easy to align. In this manuscript, we propose and demonstrate a nano-displacement measurement system based on WSI-OAM. A resolution of 0.1 nm with an uncertainty of 0.013 nm is achieved with measurement accuracy higher than 99.87% and linearity close to 99%. This work offers a practical approach to miniaturize and integrate OAM interferometers in metrology.

[Etiology composition and prognosis of pediatric chronic critical illness in a pediatric intensive care unit]. / å„¿ç«¥é‡ç—‡ç›‘æŠ¤å®¤å„¿ç«¥æ ¢æ€§å±é‡ç—‡çš„ç— å› ç»„æˆåŠé¢„åŽåˆ†æž.

OBJECTIVES: To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS: The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.

[Comparison of the impact of different fat emulsions on clinical outcomes in preterm infants with varying duration of parenteral nutrition: a randomized controlled multicenter study]. / ä¸¤ç§è„‚è‚ªä¹³å‰‚ä¸åŒè‚ å¤–è¥å »æ—¶é—´å¯¹æ—©äº§å„¿ä¸´åºŠç»“å±€å½±å“çš„æ¯”è¾ƒï¼šä¸€é¡¹éšæœºå¯¹ç §å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To compare the impact of two types of fat emulsion on clinical outcomes in preterm infants with varying duration of parenteral nutrition (PN). METHODS: Preterm infants meeting the inclusion criteria were randomly assigned to two groups: medium/long-chain triglyceride fat emulsion (referred to as MCT/LCT) group or multi-oil fat emulsion (containing soybean oil, medium-chain triglycerides, olive oil, and fish oil; referred to as SMOF) group. The infants were stratified into groups based on the duration of PN (15-21 days, 22-28 days, and ≥29 days). Clinical characteristics, nutritional status, biochemical indicators, and clinical outcomes were compared between the two groups. RESULTS: Compared with the MCT/LCT group, the SMOF group had lower peak levels of triglyceride during the hospital stay in preterm infants with PN of 15-21 days, 22-28 days, and ≥29 days, respectively (P<0.05). Logistic regression trend analysis showed that with a longer duration of PN, the risk of parenteral nutrition-associated cholestasis (PNAC) and bronchopulmonary dysplasia (BPD) significantly increased in the MCT/LCT group (P<0.05), while the risk of brain injury did not significantly change (P>0.05). In the SMOF group, the risks of PNAC and BPD did not significantly change with a longer duration of PN (P>0.05), but the risk of brain injury significantly decreased (P=0.006). CONCLUSIONS: Compared to MCT/LCT, SMOF have better lipid tolerance. With a longer duration of PN, SMOF does not increase the risks of PNAC and BPD and had a protective effect against brain injury. This suggests that in preterm infants requiring long-term PN, the use of SMOF is superior to MCT/LCT.

Asthma control conundrum in clinical practice - Data from a two-stage Delphi survey and literature review.

Definitions and measures of asthma control used in clinical trials and practice often vary, as highlighted in the manuscript, "Is asthma control more than just an absence of symptoms? An expert consensus statement". Furthermore, the authors discussed differences between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma. Given these disparities, there is a need for consensus regarding what constitutes well-controlled asthma and, especially, how best it can be measured and recorded. In the current work, we describe our data and provide more detail on the methodology from a two-stage Delphi survey and a structured literature review, which were designed to reach a consensus definition of asthma control and alleviate misalignments between patients and HCPs. Survey data were collected using a two-stage Delphi technique; a method used to collate expert opinions over a series of sequential questionnaires to reach a consensus. The collated Delphi survey data were compared with results from a comprehensive, structured literature review of 216 publications, to assess if there was a correlation between existing guidance and measures of asthma control used in clinical trials and standard clinical practice. In order to collate and interpret findings from the Delphi survey, responses from 82 panelists (73 HCPs and 9 authors) were qualitatively analyzed, quantitatively categorized, and presented as percentages or counts in Excel databases, which are detailed in the current work. Searches conducted using PubMed and Cochrane identified 664 manuscripts, and Embase was used to identify 89 congress abstracts. After applying a stringent screening method using predefined key words, the structured literature review consisted of 185 peer-reviewed manuscripts and 31 congress abstracts, and assessed existing guidance and measures of asthma control used in clinical trials. In this publication, we provide further insight into the predefined keywords, search strings, and strategy applied to identify manuscripts and congress abstracts for inclusion/exclusion, and detail methods for data extraction. Together, the data from the Delphi survey and structured literature review aimed to provide greater insights into challenges and approaches in achieving asthma control in clinical practice, with the potential for results to be used to guide a universally accepted definition and measure of asthma control that can be used and understood by patients, HCPs, and researchers. Qualitative and quantitative methodology and analysis from the Delphi survey and literature review search strategy can potentially be used to identify disparities and explore expert opinion and relevant literature in other therapeutic areas to guide a consensus where disparities exist.

Integrated Analysis of Non-Coding RNA and mRNA Expression Profiles in Exosomes from Lung Tissue with Sepsis-Induced Acute Lung Injury.

Background: Acute lung injury (ALI) is associated with a high mortality rate; however, the underlying molecular mechanisms are poorly understood. The purpose of this study was to investigate the expression profile and related networks of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in lung tissue exosomes obtained from sepsis-induced ALI. Methods: A mouse model of sepsis was established using the cecal ligation and puncture method. RNA sequencing was performed using lung tissue exosomes obtained from mice in the sham and CLP groups. Hematoxylin-eosin staining, Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction, and nanoparticle tracking analysis were performed to identify relevant phenotypes, and bioinformatic algorithms were used to evaluate competitive endogenous RNA (ceRNA) networks. Results: Thirty lncRNA-miRNA-mRNA interactions were identified, including two upregulated lncRNAs, 30 upregulated miRNAs, and two downregulated miRNAs. Based on the expression levels of differentially expressed mRNAs(DEmRNAs), differentially expressed LncRNAs(DELncRNAs), and differentially expressed miRNAs(DEmiRNAs), 30 ceRNA networks were constructed. Conclusion: Our study revealed, for the first time, the expression profiles of lncRNA, miRNA, and mRNA in exosomes isolated from the lungs of mice with sepsis-induced ALI, and the exosome co-expression network and ceRNA network related to ALI in sepsis.

Effect of WISP1 on paraquat-induced EMT.

BACKGROUND: Paraquat (PQ) can induce pulmonary fibrosis (PF) by modulating epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, but the molecular mechanism is unknown. In this paper, the role of Wnt-inducible signaling protein-1 (WISP1) in PQ-induced EMT was inspected. METHODS: The morphology, apoptosis, and mortality of A549 cells were observed through a microscope. The mRNA and protein levels of WISP1, E-cadherin, and Vimentin were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. RESULTS: With the increase of PQ concentration, the morphology of A549 cells was apparently changed, cell apoptosis and mortality were enhanced. Besides, the E-cadherin abundance was reduced (p < 0.01), however, WISP1 and Vimentin contents were boosted after PQ treatment (p < 0.01). With the increase of PQ treatment time, the epithelial index of cells first increased and then decreased. The expression of WISP1 gene increased significantly with the increase of PQ treatment time (p < 0.01). Silence of WISP1 abolished the effect of PQ treatment on E-cadherin and Vimentin levels (p < 0.01). Downregulation of WISP1 curbed morphology change and PQ-induced EMT in A549 cells. CONCLUSION: Knockdown of WISP1 inhibited PQ-induced EMT in A549 cells. This conclusion might provide a new therapeutic target for PQ poisoning treatment.

[Research Progress in Adjacent Anatomical Structure and Location of Cricothyroid Membrane].

Cricothyroid membrane puncture and incision,the key techniques to save the lives of the patients in the Can't Intubate,Can't Oxygenate (CICO) emergency,need to be mastered by all the airway management staff.However,the decision to carry out cricothyroid membrane puncture or incision is often delayed due to the unfamiliarity with the adjacent anatomical structure of the cricothyroid membrane and the inability to accurately locate the cricothyroid membrane.As a result,serious complications and rescue failure occur.Therefore,airway management staff should be familiar with the adjacent structure and positioning methods of the cricothyroid membrane,so as to improve the success rate of emergency airway rescue,reduce complications,and protect the airway and life safety of the patients.

Characterization, Structure, and Reactivity of Hydroxyl groups on Metal-Oxide Cluster Nodes of Metal-Organic Frameworks: Structural Diversity and Keys to Reactivity and Catalysis.

Among the most stable metal-organic frameworks (MOFs) are those incorporating nodes that are metal oxide clusters with frames such as Zr6 O8 . This review is a summary of the structure, bonding, and reactivity of MOF node hydroxyl groups, emphasizing those bonded to nodes containing aluminum and zirconium ions. Hydroxyl groups are often present on these nodes, sometimes balancing the charges of the metal ions. They arise during MOF syntheses in aqueous media or in post-synthesis treatments. They have been identified with infrared and 1 H nuclear magnetic resonance spectroscopies and characterized by their reactivities with polar compounds such as alcohols. Terminal OH, paired µ2 -OH, and aqua groups on nodes are catalytic sites in numerous reactions. Relatively unreactive hydroxyl groups (such as isolated µ2 -OH groups) may replace reactive groups and inhibit catalysis; some node hydroxyl groups (e.g., µ3 -OH) are mere spectators in catalysis. There are similarities between MOF node hydroxyl groups and those on the surfaces of bulk metal oxides, zeolites, and enzymes, but the comparisons are mostly inexact, and much remains to be understood about MOF node hydroxyl group chemistry. We posit that understanding and controlling this chemistry will lead to tailored MOFs and improved adsorbents and catalysts. This article is protected by copyright. All rights reserved.

Sonodynamic Therapy of NRP2 Monoclonal Antibody-Guided MOFs@COF Targeted Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis to Induce Autophagy-Dependent Ferroptosis.

The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron-based metal organic framework (Fe-MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer-specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation. This system can overcome gemcitabine resistance in pancreatic cancer and reduce its toxicity to non-targeted cells and tissues. In a mechanistic cascade, the release of ROS activates the mitochondrial transition pore (MPTP), leading to the release of Ca2+ and induction of endoplasmic reticulum (ER) stress. Therefore, microtubule-associated protein 1A/1B-light chain 3 (LC3) is activated, promoting lysosomal autophagy. This process also induces autophagy-dependent ferroptosis, aided by the upregulation of Nuclear Receptor Coactivator 4 (NCOA4). This mechanism increases the sensitivity of pancreatic cancer cells to chemotherapeutic drugs and increases mitochondrial and DNA damage. The findings demonstrate the potential of GDMCN2 nanocages as a new avenue for the development of cancer therapeutics.

RING finger ubiquitin E3 ligase CsCHYR1 targets CsATAF1 for degradation to modulate the drought stress response of cucumber through the ABA-dependent pathway.

CsCHYR1 (CHY ZINC-FINGER AND RING PROTEIN1) encodes a RING (Really Interesting New Gene) finger E3 ubiquitin ligase involved in ubiquitin-mediated protein degradation and plays an important role for cucumber to resist drought stress. Here, we obtain one of the candidate proteins CsCHYR1 that probably interacts with CsATAF1 by yeast-two hybrid screening. Subsequently, it is verified that CsCHYR1 interacts with CsATAF1 and has self-ubiquitination activity. When the cysteine residue at 180 in the RING domain of CsCHYR1 is replaced by serine or alanine, ubiquitin could not be transported from E2 to the substrate. CsCHYR1 ubiquitinates CsATAF1 and affects the stability of CsATAF1 when plants are subjected to drought stress. The expression level of CsCHYR1 is increased by 4-fold after ABA treatment at 9 h. The Atchyr1 mutants perform an ABA-hyposensitive phenotype and have a lower survival rate than Col-0 and CsCHYR1 Atchyr1 lines. In addition, CsCHYR1 interacts with CsSnRK2.6. Therefore, our study reveals a CsSnRK2.6-CsCHYR1-CsATAF1 complex to promote the drought stress response by decreasing CsATAF1 protein accumulation and inducing stomatal closure. Those findings provide new ideas for cucumber germplasm innovation from the perspective of biochemistry and molecular biology.

NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates.

Cellular senescence, characterized by stable cell cycle arrest, plays an important role in aging and age-associated pathologies. Eliminating senescent cells rejuvenates aged tissues and ameliorates age-associated diseases. Here, we identified that natural killer group 2 member D ligands (NKG2DLs) are up-regulated in senescent cells in vitro, regardless of stimuli that induced cellular senescence, and in various tissues of aged mice and nonhuman primates in vivo. Accordingly, we developed and demonstrated that chimeric antigen receptor (CAR) T cells targeting human NKG2DLs selectively and effectively diminish human cells undergoing senescence induced by oncogenic stress, replicative stress, DNA damage, or P16INK4a overexpression in vitro. Targeting senescent cells with mouse NKG2D-CAR T cells alleviated multiple aging-associated pathologies and improved physical performance in both irradiated and aged mice. Autologous T cells armed with the human NKG2D CAR effectively delete naturally occurring senescent cells in aged nonhuman primates without any observed adverse effects. Our findings establish that NKG2D-CAR T cells could serve as potent and selective senolytic agents for aging and age-associated diseases driven by senescence.

Sensorineural Hearing Loss in Autoimmune Diseases: A Systematic Review and Meta-analysis.

Autoimmune diseases may cause various kinds of conflicts in and outside the target organ, and some evidence brings forward the suggestion that autoimmune diseases may damage the auditory nerve and cause sensorineural hearing loss. However, this relationship is not clearly defined yet. Therefore, the aim of this study was to assess sensorineural hearing loss in autoimmune diseases through systematic review and metaanalysis. The literature databases of PubMed, Google Scholar, Scopus, Web of knowledge, and Cochrane library were thoroughly searched, and a meta-analysis study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Eighteen articles were included, involving 27 859 cases affected by autoimmune diseases. The prevalence of sensorineural hearing loss in systemic lupus erythematosus cases was 21.26 [3.80, 38.71]%, which was significant, and pooled analysis of odds ratio observed in individual studies showed that the odds of sensorineural hearing loss prevalence was 12.11 [7.4, 24.12] (P < .001). The prevalence of sensorineural hearing loss in rheumatoid arthritis cases was 16.14 [-9.03, 41.31]%, which was significant, and pooled analysis of odds ratio observed in individual studies showed that the odds of sensorineural hearing loss prevalence was 2.23 [1.84, 2.32] (P < .001). In vitiligo cases, the prevalence of sensorineural hearing loss was 38.80 [22.36, 55.25]%, which was significant, and pooled analysis of odds ratio observed in individual studies showed that the odds of sensorineural hearing loss prevalence was 5.82 [3.74, 9.68] (P < .001). The present study showed that sensorineural hearing loss is significantly related to the autoimmune diseases of systemic lupus erythematosus, rheumatoid arthritis, and vitiligo. Therefore, these cases need a routine evaluation of sensorineural hearing loss.