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Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine. [ABSTRACT FROM AUTHOR]

Transfer RNAs (tRNAs) play pivotal roles in the transmission of genetic information, and abnormality of tRNAs directly leads to translation disorders and causes diseases, including cancer. The complex modifications enable tRNA to execute its delicate biological function. Alteration of appropriate modifications may affect the stability of tRNA, impair its ability to carry amino acids, and disrupt the pairing between anticodons and codons. Studies confirmed that dysregulation of tRNA modifications plays an important role in carcinogenesis. Furthermore, when the stability of tRNA is impaired, tRNAs are cleaved into small tRNA fragments (tRFs) by specific RNases. Though tRFs have been found to play vital regulatory roles in tumorigenesis, its formation process is far from clear. Understanding improper tRNA modifications and abnormal formation of tRFs in cancer is conducive to uncovering the role of metabolic process of tRNA under pathological conditions, which may open up new avenues for cancer prevention and treatment. • tRNAs play pivotal roles in the transmission of genetic information, and abnormality of tRNAs directly leads to translation disorders and causes diseases, including cancer. • The complex modifications enable tRNA to execute its delicate biological function. Dysregulation of tRNA modifications plays an important role in carcinogenesis. • tRNAs can be cleaved into tRFs, which have been found to play vital regulatory roles in tumorigenesis. [ABSTRACT FROM AUTHOR]

Transfer RNAs (tRNAs) are a class of non-coding RNAs responsible for amino acid translocation during protein synthesis and are ubiquitously found in organisms. With certain modifications and under specific conditions, tRNAs can be sheared and fragmented into small non-coding RNAs, also known as tRNA-derived small RNAs (tDRs). With the development of high-throughput sequencing technologies and bioinformatic strategies, more and more tDRs have been identified and their functions in organisms have been characterized. tRNA and it derived tDRs, have been shown to be essential not only for transcription and translation, but also for regulating cell proliferation, apoptosis, metastasis, and immunity. Aberrant expression of tDRs is associated with a wide range of human diseases, especially with tumorigenesis and tumor progression. The tumor microenvironment (TME) is a complex ecosystem consisting of various cellular and cell-free components that are mutually compatible with the tumor. It has been shown that tDRs regulate the TME by regulating cancer stem cells, immunity, energy metabolism, epithelial mesenchymal transition, and extracellular matrix remodeling, playing a pro-tumor or tumor suppressor role. In this review, the biogenesis, classification, and function of tDRs, as well as their effects on the TME and the clinical application prospects will be summarized and discussed based on up to date available knowledge. [ABSTRACT FROM AUTHOR]

After publication of the article [1], authors found out that Fig. 1 was inadvertently replaced. [ABSTRACT FROM AUTHOR]

Background: LGBTQ+ community's higher susceptibility to worse mental health outcomes and more help-seeking barriers compared to the cis-heterosexual population. Despite the LGBTQ+ population facing higher mental health risks, there has been a dearth of research focusing on developing tailored interventions targeting them. This study aimed to assess the effectiveness of a digital multicomponent intervention in promoting help-seeking for mental health issues in LGBTQ+ young adults. Methods and findings: We recruited LGBTQ+ young adults aged between 18 and 29 who scored moderate or above on at least 1 dimension of the Depression Anxiety Stress Scale 21 and did not have help-seeking experiences in the past 12 months. Participants (n = 144) were stratified by gender assigned at birth (male/female) and randomly allocated (1:1 ratio) to the intervention or active control parallel condition by generating a random number table, so they were blinded to the intervention condition. All participants received online psychoeducational videos, online facilitator-led group discussions, and electronic brochures in December 2021 and January 2022, with the final follow-up in April 2022. The contents of the video, discussion, and brochure are help-seeking for the intervention group and general mental health knowledge for the control group. The primary outcomes were help-seeking intentions for emotional problems and suicidal ideation and attitudes toward seeking help from mental health professionals at the 1-month follow-up. The analysis was performed by including all participants based on their randomized group regardless of adherence to the protocol. A linear mixed model (LMM) was used for analysis. All models were adjusted for baseline scores. Chinese Clinical Trial Registry: ChiCTR2100053248. A total of 137 (95.1%) participants completed a 3-month follow-up, and 4 participants from the intervention condition and 3 from the control condition did not complete the final survey. Compared with the control group (n = 72), a significant improvement was found in help-seeking intentions for suicidal ideation in the intervention group (n = 70) at post-discussion (mean difference = 0.22, 95% CI [0.09, 0.36], p = 0.005), 1-month (mean difference = 0.19, 95% CI [0.06, 0.33], p = 0.018), and 3-month follow-ups (mean difference = 0.25, 95% CI [0.11, 0.38], p = 0.001). There was also a significant improvement in the intervention condition on the help-seeking intention for emotional problems at 1-month (mean difference = 0.17, 95% CI [0.05, 0.28], p = 0.013) and 3-month follow-ups (mean difference = 0.16, 95% CI [0.04, 0.27], p = 0.022) compared with the control group. Participants' depression and anxiety literacy and help-seeking encouragement related knowledge in intervention conditions showed significant improvements. There were no significant improvements in actual help-seeking behaviors, self-stigma toward seeking professional assistance, depression, and anxiety symptoms. No adverse events or side effects were observed. However, the follow-up time point was limited to 3 months which might not be long enough for drastic mindset and behavioral changes in help-seeking to occur. Conclusions: The current intervention was an effective approach in promoting help-seeking intentions, mental health literacy, and help-seeking encouragement-related knowledge. Its brief yet integrated intervention format could also be utilized in treating other imminent concerns confronted by LGBTQ+ young adults. Trial Registration: Chictr.org.cn, ChiCTR2100053248. In a randomized controlled trial, Runsen Chen and colleagues investigate the impact of a multi-component digital intervention to promote help-seeking for mental health problems and suicide in sexual and gender diverse young adults. Author summary: Why was this study done?: Members of the LGBTQ+ community, compared to their cis-heterosexual counterparts, are less likely to seek help for mental problems due to minority stress, stigma, and difficulty in acquiring sexual- and gender-affirmative care. Findings from past studies suggest that psychoeducational videos, facilitator-led group discussions, and help-seeking brochures are all key influential factors for individuals' help-seeking. Nevertheless, few studies have investigated the effectiveness of multicomponent approaches and digital online-based interventions targeted at LGBTQ+ young adults' help-seeking behaviors. What did researchers do and find?: We conducted a single-blind parallel-group randomized control trial to evaluate the efficacy of a digital online-based multicomponent intervention in promoting help-seeking among LGBTQ+ young adults with mental health problems. We included 144 participants recruited between December 3, 2021 and January 12, 2022 through online platforms who had no help-seeking experience within the past 12 months. We randomized 72 participants to the help-seeking promoting condition and compared them to 72 who received general health knowledge condition. The study was conducted over 5 months. Our findings indicated that an integrated intervention that combines psychoeducational videos, facilitator-led group discussions, and help-seeking brochures was effective in improving LGBTQ+ young adults' general help-seeking intentions. What do these findings mean?: Our study offers preliminary evidence that digital interventions can improve help-seeking for LGBTQ+ young adults with mental health difficulties. Integration of digital interventions by policymakers to care provided to LGBTQ+ young adults may help to improve help-seeking and mental health outcomes on a wider societal level. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are connected at the 3′ and 5′ ends by exon or intron cyclization, forming a complete ring structure. circRNA is more stable and conservative than linear RNA and abounds in various organisms. In recent years, increasing numbers of reports have found that circRNA plays a major role in the biological functions of a network of competing endogenous RNA (ceRNA). circRNAs can compete together with microRNAs (miRNAs) to influence the stability of target RNAs or their translation, thus, regulating gene expression at the transcriptional level. circRNAs are involved in biological processes such as tumor cell proliferation, apoptosis, invasion, and migration as ceRNAs. circRNAs, therefore, represent promising candidates for clinical diagnosis and treatment. Here, we review the progress in studying the role of circRNAs as ceRNAs in tumors and highlight the participation of circRNAs in signal transduction pathways to regulate cellular functions. [ABSTRACT FROM AUTHOR]