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The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the Kras LSL−G12D/+ Tp53 fl/fl (KP) and the Kras LSL−G12D/+ Lkb1 fl/fl (KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8 + and CD4 + T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC. Only a limited proportion of patients with non-small cell lung cancer respond to anti-PD-1/PD-L1 immunotherapy. Here, the authors show that in autochthonous models of KRAS-mutated lung cancer, CCL7 promotes cDC1 infiltration into the lungs, sustaining antitumor immune responses and potentiating anti-PD1 treatment efficacy.

Malaria associated anemia is increasingly recognized as a consequence not only of red cell destruction but of profound, parasite driven disruption of erythropoiesis within the bone marrow niche. Here, we synthesize recent in vitro , ex vivo, clinical and postmortem studies to construct a unified mechanistic framework in which four interlocking pathways converge to produce dyserythropoiesis. First, a cytokine storm dominated by IL-6, TNF-α, IFN-γ and MIF suppresses erythropoietin synthesis, upregulates hepcidin and diverts erythroid progenitors toward myeloid fate via destabilization of GATA-1. Second, hemozoin crystals catalyze Fenton chemistry and lipid peroxidation, generating 4-hydroxynonenal adducts that cripple GATA-1 and trigger mitochondrial apoptosis of erythroblasts. Third, Plasmodium parasites preferentially infect orthochromatic erythroblasts, prolonging a 10-day gametocyte maturation cycle beyond the host’s 3–4-day enucleation window and releasing extracellular vesicles that arrest terminal differentiation. Fourth, hemozoin-laden macrophages remodel erythroblastic islands, precipitating local iron restriction and sustained oxidative stress. Together these processes create a “developmental sanctuary” that favors parasite persistence while crippling host erythropoiesis. We also highlight emerging single-cell and spatial-omics technologies, together with 3-D bone-marrow organoids, as platforms for dissecting spatiotemporal parasite–host interactions and for testing niche-targeted therapies aimed at reversing ineffective erythropoiesis.

Background Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). Methods This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m 2 . LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10 6 cells/kg [range, 0.07 to 2.1 × 10 6 ]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. Results At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. Conclusions LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. Trial registration ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered

Background The increased adoption of the internet, social media, wearable devices, e-health services, and other technology-driven services in medicine and healthcare has led to the rapid generation of various types of digital data, providing a valuable data source beyond the confines of traditional clinical trials, epidemiological studies, and lab-based experiments. Methods We provide a brief overview on the type and sources of real-world data and the common models and approaches to utilize and analyze real-world data. We discuss the challenges and opportunities of using real-world data for evidence-based decision making This review does not aim to be comprehensive or cover all aspects of the intriguing topic on RWD (from both the research and practical perspectives) but serves as a primer and provides useful sources for readers who interested in this topic. Results and Conclusions Real-world hold great potential for generating real-world evidence for designing and conducting confirmatory trials and answering questions that may not be addressed otherwise. The voluminosity and complexity of real-world data also call for development of more appropriate, sophisticated, and innovative data processing and analysis techniques while maintaining scientific rigor in research findings, and attentions to data ethics to harness the power of real-world data.

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs that associate with proteins of the PIWI clade of the Argonaute family. First identified in animal germ line cells, piRNAs have essential roles in germ line development. The first function of PIWI–piRNA complexes to be described was the silencing of transposable elements, which is crucial for maintaining the integrity of the germ line genome. Later studies provided new insights into the functions of PIWI–piRNA complexes by demonstrating that they regulate protein-coding genes. Recent studies of piRNA biology, including in new model organisms such as golden hamsters, have deepened our understanding of both piRNA biogenesis and piRNA function. In this Review, we discuss the most recent advances in our understanding of piRNA biogenesis, the molecular mechanisms of piRNA function and the emerging roles of piRNAs in germ line development mainly in flies and mice, and in infertility, cancer and neurological diseases in humans.PIWI-interacting RNAs (piRNAs) are small non-coding RNAs with essential roles in germ line development through silencing of transposable elements and in regulation of protein-coding genes. Recent studies have deepened our understanding of the biogenesis and function of piRNAs and their roles in infertility, cancer and neurological diseases in humans.

Purpose The 2019 novel coronavirus (COVID-19) outbreak is projected to have adverse consequences on the global tourism and hospitality industry. This paper aims to examine how the outbreak may alter Chinese tourists’ lifestyle choices, travel behaviour and tourism preferences in the short and long term. Design/methodology/approach This paper is based on the synthesis of news broadcasted by several media outlets to be supported by an overview of the related literature on tourism marketing, tourism management and tourist behaviour. The authors’ experiences investigating trends in tourism and hospitality at the local and international level have also contributed to the study. Findings This paper predicts that COVID-19 will likely affect Chinese travellers’ consumption patterns, such as the growing popularity of free and independent travel, luxury trips and health and wellness tourism. New forms of tourism including slow tourism and smart tourism may also drive future tourism activities. Such changes are likely to force businesses to reconsider their service designs and distribution channels. Research limitations/implications While Chinese and other potential visitors rethink how they travel, professionals, too, should reflect upon how to bring positive or negative changes to the tourism industry following this pandemic. Subsequent research should also consider how to mitigate the effects of similar public health crises in the future. Practical implications Recommendations for industry practitioners and policymakers focus on tailoring travel arrangements to tourists’ backgrounds. The suggestions may help to alleviate outbreak-related stress, offer travellers newly enriching experiences and partially mitigate the effects of COVID-19 on the tourism and hospitality industry. These recommendations can also apply more broadly to global tourist markets. Social implications The COVID-19 outbreak has already brought significant impacts to nearly every society and industry. Tourism scholars and practitioners should carefully consider this tragedy and how it may inform industry and social practices. This and other public health crises represent sterling opportunities to view the industry holistically in terms of its effects on the environment, climate and travellers themselves. Originality/value This paper presumably represents a frontier study, critically examining the possible impacts of COVID-19 on Chinese travellers’ consumption patterns and how the tourism and hospitality industry may respond to such changes in the future. COVID-19: 对中国公民的生活方式和旅行可能产生的影响 摘要 预计2019年新型冠状病毒（COVID-19）爆发将对全球旅游和酒店业产生不利影响。本文预测, COVID-19可能会影响中国旅客的消费方式, 例如自由行, 豪华旅行以及健康与养生旅游的普及。包括慢速旅游和智能旅游在内的新型旅游形式也可能推动未来的旅游活动。这种变化可能促使企业重新考虑其服务设计和分销渠道。针对行业从业者和政策制定者的建议着重于根据游客的背景和需求量身定制旅行安排。我们的建议可能有助于减轻与疫情暴发导致的压力, 为旅行者提供全新的丰富体验, 并从一定程度减轻COVID-19对旅游业和酒店业的影响。这些建议还可以更广泛地应用于全球旅游市场。 关键词 COVID-19, 生活方式 旅游行为 灾后 集体主义倾向 中国 COVID-19: Efectos potenciales sobre el estilo de vida y los viajes de los ciudadanos chinos El extracto El impacto del COVID-19 se prevé importante en la actividad turística global y en la industria de la hostelería. Este artículo predice que el COVID-19 afectará con probabilidad alta los patrones de consumo de los viajeros chinos, incluyendo los cada vez más populares viajes comprados directamente por los consumidores chinos, en el segmento del lujo, y el turismo de salud y belleza. Nuevas formas de turismo, incluyendo el slow tourism, y el turismo responsable pueden convertirse en importantes tendencias de futuro igualmente. Dichos cambios llevarán con cierta seguridad a la industria a reconsiderar y adaptar su oferta de servicios en este sector, en particular su diseño y los canales de distribución utilizados. Las recomendaciones para la industria y los responsables de la política turística se alinean con una mayor proximidad de la oferta a los gustos cambiantes del consumidor. Dichas acciones ayudarán a reducir fricciones y fallos en la definición del negocio turístico, ofreciendo a los viajeros nuevas y enriquecedoras experiencias, así como podrán mitigar en parte los efectos adversos estimados del COVID-19, los cuales son relevantes a día de hoy. Así mismo, dichas recomendaciones son aplicables de una manera más global a la industria del turismo y la hospitalidad en el mercado mundial. Palabras-clave COVID-19, Estilo de vida, Conducta del viajero, Post-desastre, Orientacion collectivista, China

Background LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. Methods LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 10 6 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. Results As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. Conclusions The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.

Background: Tobacco smoke is known to contain numerous harmful chemicals, and epidemiological evidence has firmly established smoking as a potent risk factor for hypertension and myocardial infarction (MI). However, the precise mechanisms by which smoking contributes to cardiovascular disease are not fully understood. The aim of this study is to identify common molecular signatures in blood that link smoking to acute MI (AMI). Methods: We extracted transcriptome data from seven blood microarray datasets in the Gene Expression Omnibus (GEO) database, encompassing a total of 403 patients. Employing both individual dataset analysis and a combined meta‐analysis approach, we conducted a thorough examination of blood transcriptome profiles associated with AMI and smoking, uncovering numerous differentially expressed genes (DEGs). Results: Functional enrichment analysis indicated that DEGs associated with AMI and smoking were significantly enriched in overlapping biological processes, such as immune response and inflammation. Moreover, three genes—PTGDR, PYHIN1, and PRSS23—were consistently altered in both conditions and were validated as dysregulated in AMI using an independent GEO dataset. Furthermore, quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) validation further confirmed the differential expression of PYHIN1 and PRSS23 in AMI patients. Conclusions: Our findings suggest that gene expression changes induced by smoking in blood may contribute to the heightened risk of AMI. These identified genes are likely to play critical roles in the pathogenesis of AMI. Given the accessibility of peripheral blood samples, the expression levels of these genes could potentially serve as biomarkers for assessing cardiovascular health, particularly in individuals with a history of long‐term exposure to cigarette smoke.