Explore the vast range of titles available.

Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which is called abscopal effect. The view of RT as a simple local treatment has dramatically changed in recent years, and it is now widely accepted that RT can provoke a systemic immune response which gives a strong rationale for the combination of RT and immunotherapy (iRT). Nevertheless, several points remain to be addressed such as the interaction of RT and immune system, the identification of the best schedules for combination with immunotherapy (IO), the expansion of abscopal effect and the mechanism to amplify iRT. To answer these crucial questions, we roundly summarize underlying rationale showing the whole immune landscape in RT and clinical trials to attempt to identify the best schedules of iRT. In consideration of the rarity of abscopal effect, we propose that the occurrence of abscopal effect induced by radiation can be promoted to 100% in view of molecular and genetic level. Furthermore, the “radscopal effect” which refers to using low-dose radiation to reprogram the tumor microenvironment may amplify the occurrence of abscopal effect and overcome the resistance of iRT. Taken together, RT could be regarded as a trigger of systemic antitumor immune response, and with the help of IO can be used as a radical and systemic treatment and be added into current standard regimen of patients with metastatic cancer.

Lung cancer continues to pose a serious global public health challenge. Timely evidence on the global epidemiological profile of the disease is crucial to facilitate the implementation to lung cancer control efforts. This study provides updated global estimates for lung cancer incidence and mortality in 2022, along with projections for new cases and deaths up to 2050. In the population-based study, we extracted data about lung cancer new cases and deaths from GLOBOCAN 2022 database across 185 countries or territories. We analyzed age-standardized rates by sex, country, region, and human development index (HDI). Projected new cases and deaths for 2050 were estimated using global demographic projections. In 2022, lung cancer stood as the most frequently diagnosed cancer and the primary cause of cancer-related deaths on a global scale with approximately 2.48 million new cases and 1.8 million deaths, respectively. The incidence and mortality rates of lung cancer exhibited disparities in sex and world regions. Furthermore, incidence and mortality rates increasing as HDI increased. If the incidence and mortality rates remain stable as in 2022, the burden of lung cancer is projected to increase to 4·62 million new cases and 3·55 million deaths by 2050. Lung cancer is the predominant form of cancer and the foremost contributor to cancer-related mortality in 2022 with notable geographical, sex, and socioeconomic disparities. •Lung cancer is the leading global cause of cancer incidence and mortality, with a strong link to HDI.•Significant sex disparity exists, with higher rates in males.•Urgent, customized strategies are needed to counteract the escalating lung cancer burden and health inequities worldwide.

Electrocatalytic C-N coupling from carbon dioxide and nitrate provides a sustainable alternative to the conventional energy-intensive urea synthetic protocol, enabling wastes upgrading and value-added products synthesis. The design of efficient and stable electrocatalysts is vital to promote the development of electrocatalytic urea synthesis. In this work, copper phthalocyanine (CuPc) is adopted as a modeling catalyst toward urea synthesis owing to its accurate and adjustable active configurations. Combining experimental and theoretical studies, it can be observed that the intramolecular Cu-N coordination can be strengthened with optimization in electronic structure by amino substitution (CuPc-Amino) and the electrochemically induced demetallation is efficiently suppressed, serving as the origination of its excellent activity and stability. Compared to that of CuPc (the maximum urea yield rate of 39.9 ± 1.9 mmol h −1 g −1 with 67.4% of decay in 10 test cycles), a high rate of 103.1 ± 5.3 mmol h −1 g −1 and remarkable catalytic durability have been achieved on CuPc-Amino. Isotope-labelling operando electrochemical spectroscopy measurements are performed to disclose reaction mechanisms and validate the C-N coupling processes. This work proposes a unique scheme for the rational design of molecular electrocatalysts for urea synthesis. Electrocatalytic C-N coupling of carbon dioxide and nitrate offers a sustainable alternative to traditional urea production. Here the authors report amino substitution in copper phthalocyanine for enhanced urea electrosynthesis.

Effective pain control during spinal anesthesia positioning remains a clinical challenge in elderly patients undergoing total hip arthroplasty. The pericapsular nerve group block, a novel ultrasound-guided regional anesthesia technique, has shown promise for alleviating hip pain, yet the optimal concentration of local anesthetics for this approach remains unclear. In this randomized, observer-blinded clinical trial involving 102 patients, we compared the analgesic efficacy of two concentrations of ropivacaine (0.375% vs. 0.5%) administered via pericapsular nerve group block prior to spinal anesthesia. Patients receiving 0.5% ropivacaine reported significantly lower pain scores during positioning and demonstrated prolonged postoperative analgesia up to 48 hours, without a corresponding increase in adverse events. Both concentrations improved positioning quality, reduced opioid requirements, and enhanced recovery compared to controls who received standard intravenous analgesic supplementation (including preoperative midazolam and ketorolac, and postoperative sufentanil PCA), though the higher concentration yielded modest additional benefits. These findings suggest that a 0.5% ropivacaine pericapsular nerve group block may offer superior perioperative analgesia for hip arthroplasty without compromising safety, while highlighting the need to balance analgesic potency with potential motor effects. This study informs optimization of nerve block protocols to improve perioperative outcomes in a high-risk surgical population. This study informs optimization of nerve block protocols to improve perioperative outcomes in a high-risk surgical population. The trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2400089440).

Radiation-induced lung injury (RILI) is a form of radiation damage to normal lung tissue caused by radiotherapy (RT) for thoracic cancers, which is most commonly comprised of radiation pneumonitis (RP) and radiation pulmonary fibrosis (RPF). Moreover, with the widespread utilization of immunotherapies such as immune checkpoint inhibitors as first- and second-line treatments for various cancers, the incidence of immunotherapy-related lung injury (IRLI), a severe immune-related adverse event (irAE), has rapidly increased. To date, we know relatively little about the underlying mechanisms and signaling pathways of these complications. A better understanding of the signaling pathways may facilitate the prevention of lung injury and exploration of potential therapeutic targets. Therefore, this review provides an overview of the signaling pathways of RILI and IRLI and focuses on their crosstalk in diverse signaling pathways as well as on possible mechanisms of adverse events resulting from combined radiotherapy and immunotherapy. Furthermore, this review proposes potential therapeutic targets and avenues of further research based on signaling pathways. Many new studies on pyroptosis have renewed appreciation for the value and importance of pyroptosis in lung injury. Therefore, the authors posit that pyroptosis may be the common downstream pathway of RILI and IRLI; discussion is also conducted regarding further perspectives on pyroptosis as a crucial signaling pathway in lung injury treatment.

Quasimodular forms were first studied systematically in the context of counting torus coverings. Here we show that a weighted version of these coverings with Siegel-Veech weights also provides quasimodular forms. We apply this to prove conjectures of Eskin and Zorich on the large genus limits of Masur-Veech volumes and of Siegel-Veech constants. In Part I we connect the geometric definition of Siegel-Veech constants both with a combinatorial counting problem and with intersection numbers on Hurwitz spaces. We also introduce certain modified Siegel-Veech weights whose generating functions will later be shown to be quasimodular. Parts II and III are devoted to the study of the (quasi) modular properties of the generating functions arising from weighted counting of torus coverings. These two parts contain little geometry and can be read independently of the rest of the paper. The starting point is the theorem of Bloch and Okounkov saying that certain weighted averages, called 𝑞-brackets, of shifted symmetric functions on partitions are quasimodular forms. In Part II we give an expression for the growth polynomials (a certain polynomial invariant of quasimodular forms) of these 𝑞-brackets in terms of Gaussian integrals, and we use this to obtain a closed formula for the generating series of cumulants that is the basis for studying large genus asymptotics. In Part III we show that the even hook-length moments of partitions are shifted symmetric polynomials, and we prove a surprising formula for the 𝑞-bracket of the product of such a hook-length moment with an arbitrary shifted symmetric polynomial as a linear combination of derivatives of Eisenstein series. This formula gives a quasimodularity statement also for the (−2)-nd hook-length moments by an appropriate extrapolation, and this in turn implies the quasimodularity of the Siegel-Veech weighted counting functions. Finally, in Part IV these results are used to give explicit generating functions for the volumes and Siegel-Veech constants in the case of the principal stratum of abelian differentials. The generating functions have an amusing form in terms of the inversion of a power series (with multiples of Bernoulli numbers as coefficients) that gives the asymptotic expansion of a Hurwitz zeta function. To apply these exact formulas to the Eskin-Zorich conjectures on large genus asymptotics (both for the volume and the Siegel-Veech constant) we provide in a separate appendix a general framework for computing the asymptotics of rapidly divergent power series.

Colorectal cancer (CRC) is one of the most devastating diseases that accounts for numerous deaths worldwide. Tumor cell-autonomous pathways, such as the oncogenic signaling activation, significantly contribute to CRC progression and metastasis. Recent accumulating evidence suggests that the CRC microenvironment also profoundly promotes or represses this process. As the roles of the tumor microenvironment (TME) in CRC progression and metastasis is gradually uncovered, the importance of these non-cell-autonomous signaling pathways is appreciated. However, we are still at the beginning of this TME function exploring process. In this review, we summarize the current understanding of the TME in CRC progression and metastasis by focusing on the gut microbiota and host cellular and non-cellular components. We also briefly discuss TME-remodeling therapies in CRC.

Hypertension (HTN) is prevalent in non-small cell lung cancer (NSCLC) patients, yet the cardioprotective and survival benefits of β-adrenergic blockers during radiotherapy (RT) remain underexplored. We analyzed data from a Chinese clinical cohort of 750 patients with stage IIIA to IIIB NSCLC and HTN receiving RT between 2014 and 2018. The findings were further validated using data from the NHANES database. In Chinese clinical cohort, β-adrenergic blockers were associated with improved OS (β-adrenergic blockers: median overall survival (mOS) 17.64 months, 95% CI, 15.95–19.33; no β-adrenergic blockers: mOS 13.16 months, 95% CI, 12.62–13.70; p  < 0.0001) and PFS (β-adrenergic blockers: median progression-free survival (mPFS) 7.50 months, 95% CI, 6.50–8.50; without β-adrenergic blockers: mPFS 4.91 months, 95% CI, 4.53–5.31; p  < 0.0001). Simultaneously, in the NHANES database, the utilization of β-adrenergic blockers exhibited no discernible impact on OS within the entire tumor population, as evidenced by the Kaplan-Meier curve, which revealed no statistically significant difference between the two groups ( p  = 0.254). β-adrenergic blockers may improve OS and PFS in patients with HTN and NSCLC undergoing RT. β-adrenergic blockers show potential and warrant further investigation in the context of RT.

Background Peripheral arterial disease (PAD) is a common cause of disability and mortality. The reconstruction of blood circulation presents to be the key to treatment, which can be achieved by surgery and interventional therapy. Since 40% patients have lost the chance for the therapy, a new method is needed to reduce the amputation and mortality rate for “no-option” patients. The objective of our systematic review and meta-analysis was to evaluate the efficacy and safety of autologous implantation of stem cells in patients with PAD critically, compared with active controls and placebo. Methods Randomized controlled trials (RCTs) of autologous implantation of stem cells compared with placebo and control for PAD were included. Electronic medical databases including MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), and ClinicalTrials.gov were searched from initial period to September 2018. Independently, two reviewers screened citations, extracted data, and assessed the risk of bias according to the criteria of the Cochrane handbook. The quality of evidence was evaluated by GRADE evidence profile. The primary outcomes consisted of amputation rate, major amputation rate, ulcer healing rate, and side effects. The second outcomes included ankle-brachial index (ABI), transcutaneous oxygen tension (TcO2), pain-free walking distance (PFWD), and rest pain score. Statistical analysis was conducted via RevMan 5.3 and Stata 12.0. Results According to the twenty-seven RCTs, 1186 patients and 1280 extremities were included and the majority of studies showed a high risk of bias. Meta-analysis indicated that autologous stem cell therapy was more effective than conventional therapy on the healing rate of ulcers [OR = 4.31 (2.94, 6.30)]. There was also significant improvement in ABI [MD = 0.13 (0.10, 0.17)], TcO2 [MD = 0.13 (0.10, 0.17)], and PFWD [MD = 178.25 (128.18, 228.31)] while significant reduction was showed in amputation rate [OR = 0.50 (0.36, 0.69)] and rest pain scores [MD = − 1.61 (− 2.01, − 1.21)]. But the result presented no significant improvement in major limb salvage [0.66 (0.42, 1.03)]. Besides, stem cell therapy could reduce the amputation rate [OR = 0.50 (0.06, 0.45] and improve the ulcer healing rate [OR = 4.34 (2.96, 6.38] in DM subgroup. Eight trials reported the side effects of autologous stem cell therapy, and no serious side effects related to stem cells were reported. GRADE evidence profile showed all the quality evidence of outcomes were low. Conclusions Based on the review, autologous stem cell therapy may have a positive effect on “no-option” patients with PAD, but presented no significant improvement in major limb salvage. However, the evidence is insufficient to prove the results due to high risk of bias and low-quality evidence of outcomes. Further researches of larger, randomized, double-blind, placebo-controlled, and multicenter trials are still in demand.

Emerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.