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The trRosetta (transform-restrained Rosetta) server is a web-based platform for fast and accurate protein structure prediction, powered by deep learning and Rosetta. With the input of a protein’s amino acid sequence, a deep neural network is first used to predict the inter-residue geometries, including distance and orientations. The predicted geometries are then transformed as restraints to guide the structure prediction on the basis of direct energy minimization, which is implemented under the framework of Rosetta. The trRosetta server distinguishes itself from other similar structure prediction servers in terms of rapid and accurate de novo structure prediction. As an illustration, trRosetta was applied to two Pfam families with unknown structures, for which the predicted de novo models were estimated to have high accuracy. Nevertheless, to take advantage of homology modeling, homologous templates are used as additional inputs to the network automatically. In general, it takes ~1 h to predict the final structure for a typical protein with ~300 amino acids, using a maximum of 10 CPU cores in parallel in our cluster system. To enable large-scale structure modeling, a downloadable package of trRosetta with open-source codes is available as well. A detailed guidance for using the package is also available in this protocol. The server and the package are available at https://yanglab.nankai.edu.cn/trRosetta/ and https://yanglab.nankai.edu.cn/trRosetta/download/ , respectively. The trRosetta server, a web-based platform for fast and accurate protein structure prediction, is powered by deep learning and Rosetta. This protocol includes procedures for using the web-based server as well as the standalone package.

RNA 3D structure prediction is a long-standing challenge. Inspired by the recent breakthrough in protein structure prediction, we developed trRosettaRNA, an automated deep learning-based approach to RNA 3D structure prediction. The trRosettaRNA pipeline comprises two major steps: 1D and 2D geometries prediction by a transformer network; and 3D structure folding by energy minimization. Benchmark tests suggest that trRosettaRNA outperforms traditional automated methods. In the blind tests of the 15 th Critical Assessment of Structure Prediction (CASP15) and the RNA-Puzzles experiments, the automated trRosettaRNA predictions for the natural RNAs are competitive with the top human predictions. trRosettaRNA also outperforms other deep learning-based methods in CASP15 when measured by the Z-score of the Root-Mean-Square Deviation. Nevertheless, it remains challenging to predict accurate structures for synthetic RNAs with an automated approach. We hope this work could be a good start toward solving the hard problem of RNA structure prediction with deep learning. Here, authors develop trRosettaRNA, a deep learning-based approach for predicting RNA 3D structures. Blind tests demonstrate that the automated predictions compete effectively with top human predictions on natural RNAs.

Long noncoding RNAs (lncRNAs), a class of noncoding RNAs exceeding 200 nucleotides in length, play critical roles in regulating diverse biological processes and gene expression. Emerging evidence highlights their significant association with cancer occurrence, progression, prognosis, and therapeutic resistance, positioning lncRNAs as promising molecular targets for tumor detection and treatment. Ferroptosis, a regulated form of cell death characterized by the accumulation of iron‐dependent lipid peroxides, has gained attention as a potential therapeutic strategy for cancer, complementing existing modalities such as surgery, chemotherapy, radiotherapy, hormone therapy, and targeted molecular therapy. Recent research demonstrates that lncRNAs modulate ferroptosis in solid tumors, thereby influencing tumor cell invasion, metastasis, and proliferation. Inducing ferroptosis has been shown to inhibit tumor growth, reduce chemoresistance, and enhance radiotherapy efficacy. This review explores recent advancements in understanding the role of lncRNAs in tumor ferroptosis, with a focus on their involvement in iron metabolism and their potential as therapeutic targets in cancer combination therapies. Long noncoding RNAs (lncRNAs) play pivotal roles in regulating gene expression and are closely associated with cancer progression, prognosis, and therapeutic resistance. This review highlights recent advancements in understanding how lncRNAs modulate ferroptosis, a regulated form of cell death characterized by iron‐dependent lipid peroxidation, influencing tumor invasion, metastasis, and proliferation. These findings suggest that targeting lncRNAs and ferroptosis could offer novel approaches for cancer therapy.

Central nervous system (CNS) lesions are major causes of human death and disability worldwide, and they cause different extents of motor and sensory dysfunction in patients. Thus, it is crucial to develop new effective neuroprotective drugs and approaches targeted to the heterogeneous nature of CNS injury and disease. L-serine is an indispensable neurotrophic factor and a precursor for neurotransmitters. Although L-serine is a native amino acid supplement, its metabolic products have been shown to be essential not only for cell proliferation but also for neuronal development and specific functions in the brain. Growing evidence has suggested that L-serine regulates the release of several cytokines in the brain under some neuropathological conditions to recover cognitive function, improve cerebral blood flow, inhibit inflammation, promote remyelination and exert other neuroprotective effects on neurological injury. L-serine has also been used to treat epilepsy, schizophrenia, psychosis, and Alzheimer’s Disease as well as other neurological diseases. Furthermore, the dosing of animals with L-serine and human clinical trials investigating the therapeutic effects of L-serine generally support the safety of L-serine. The high significance of this review lies in its emphasis on the therapeutic potential of using L-serine as a general treatment for numerous CNS diseases and injuries. Because L-serine performs a broad spectrum of functions, it may be clinically used as an effective neuroprotective agent.

Amid accelerating global urbanization, the Qinghai–Tibet Plateau, as a repository of multi-ethnic architectural heritage, plays a crucial role in preserving plateau cultural diversity and sustaining harmonious human–environment relationships. A critical research gap persists, however, in the systematic, comparable, and quantitative assessment of urban architectural character across plateau towns, particularly in high-altitude, ecologically sensitive, and multi-ethnic regions such as Haixi Mongol and Tibetan Autonomous Prefecture. This study takes the Haixi Mongol and Tibetan Autonomous Prefecture as a case to address the specific paradox between the homogenization of urban architectural styles and the erosion of cultural authenticity in plateau towns. We develop and apply an innovative three-dimensional evaluation model—encompassing natural substrate, built environment, and cultural context—to 22 towns. For the first time in research on this region, a chained methodological approach integrating descriptive statistics, principal component analysis (PCA), and cluster analysis is employed to systematically examine the spatial differentiation of architectural character. The analysis reveals three key findings. First, it delineates a regional composite landscape characterized by mountain-basin enclosures, seasonal arid rivers and lakes, small-scale towns with expansive layouts, and multi-ethnic cultural fusion. Second, it identifies a clear ternary differentiation in urban style dominance: nine towns are nature-dominated, nine are human-made (built environment) dominated, and only four are culture-dominated, quantitatively highlighting a significant weakness in the cultural dimension. Third, cluster analysis objectively classifies the towns into eight distinct character groups—for instance, Category I towns exhibit strong architectural regionalism and traditional continuity, whereas Category V towns integrate modern relics with adjacent mountain-water features. Methodologically, this study contributes by providing a replicable, chained quantitative framework that addresses a critical gap in comparative urban studies of high-altitude, underdeveloped regions. Empirically, it reveals the specific “nature > human-made > culture” dominance pattern in Haixi and offers a scientific foundation for formulating differentiated conservation and development strategies tailored to distinct town types in the ecologically fragile areas of western China.

Background In 2016, the “universal two-child” policy, allowing each couple to have two children, was introduced in China. The characteristic change of the long-term period after the implementation of the universal two-child policy was unclear. We studied trends in the obstetric characteristics and their potential impact on the rates of cesarean section and preterm birth in the era of China’s universal two-child policy. Methods A tertiary center-based study (2010–2021) retrospectively focused single high-risk pregnancies who delivered from the one-child policy period (OCP, 2010–2015) to the universal two-child policy period (TCP, 2016–2021). A total of 39, 016 pregnancies were enrolled. Maternal demographics, complications, delivery mode and obstetric outcomes were analyzed. Furthermore, logistic regression analysis was used to explore the association between the cesarean section rate, preterm birth and implementation of the universal two-child policy, adjusting maternal age, parity, and fetal distress. Results Ultimately a total of 39,016 pregnant women met the criteria and were included in this analysis. The proportion of women with advanced maternal age (AMA) increased from 14.6% in the OCP to 31.6% in the TCP. The number of multiparous women increased 2-fold in the TCP. In addition, the overall rate of cesarean section significantly decreased over the policy change, regardless of maternal age, whereas the risk of preterm birth significantly increased in the TCP. Adjusting for maternal age, parity and fetal distress, the universal two-child policy showed a significantly favorable impact on the cesarean section rate (RR 0.745, 95%CI (0.714–0.777), P  < 0.001). Compared to the OCP group, a higher increase in fetal distress and premature rupture of membranes (PROM) were observed in the TCP group. In pregnancies with AMA, there was no increase in the risk of postpartum hemorrhage, whereas more women who younger than 35 years old suffered from postpartum hemorrhage in TCP. The logistic regression model showed that the universal two-child policy was positively associated with the risk of postpartum hemorrhage (RR: 1.135, 95%CI: 1.025–1.257, P  = 0.015). Conclusions After the implementation of the universal two-child policy in China, the rate of the cesarean section significantly decreased, especially for women under 35 years old. However, the overall risk of postpartum hemorrhage increased in women under 35 years old, while there was no change in women with AMA. Under the new population policy, the prevention of postpartum hemorrhage in the young women should not be neglected.

The only vaccine against Haemonchus contortus is limited by short-lived antibody persistence and the need for frequent booster immunizations. This study leveraged the advantages of nano-adjuvants in enhancing antigen presentation and immune regulation to evaluate the efficacy of novel adjuvants (IMX, AddaS03) and the conventional QuilA combined with H11 protein. Goats were divided into four groups (IMX + H11, AddaS03 + H11, QuilA + H11, and infected control). They were immunized three times and challenged with 6000 infective third-stage larvae (iL3s) of H. contortus on the day of the third immunization, with the experiment lasting for 98 days. The results showed that vaccination with IMX + H11 conferred the strongest protection, demonstrating 88.3% efficacy in fecal egg count (FEC) reduction and 75.8% efficacy against worm burden, followed by QuilA + H11 (85.2% FEC reduction and 68% worm burden reduction) and AddaS03 + H11 (79.4% FEC reduction and 61.3% worm burden reduction). Serum IgG analysis revealed high antibody levels in all immunized groups. Cytokine detection found that IMX + H11 significantly upregulated IL-2 and IFN-γ expression in PBMCs and TNF-α expression in splenocytes, activating Th1-type responses and immune memory. QuilA + H11 showed weaker Th1 activation, and AddaS03 + H11 faced limitations due to insufficient antibody persistence for long-term protection. These findings suggest that IMX can induce highly efficient humoral and cellular immunity, providing a new direction for the optimization of H. contortus vaccines and suggesting the importance of nano-adjuvants for precise regulation of immune patterns.

Non-small cell lung cancer (NSCLC) represents the most prevalent histological subtype of lung cancer. Within this disease, the MET gene emerges as a critical therapeutic target, exhibiting various forms of dysregulation. Although MET tyrosine kinase inhibitors, HGF/c-MET targeting antibodies, and antibody-drug conjugates constitute the primary treatment modalities for patients with MET-altered NSCLC, numerous questions remain regarding their optimal application. The advent of immunotherapy holds promise for enhancing therapeutic outcomes in patients with MET-altered NSCLC. MET mutations can reshape the tumor immune microenvironment of NSCLC by reducing tumor immunogenicity, inducing exhaustion in immune-activated cells, and promoting immune evasion, which are crucial for modulating treatment responses. Furthermore, we emphasize the promising synergy of immunotherapy with emerging treatments and the challenges and opportunities in refining these approaches to improve patient outcomes.

Esophageal cancer (EC) is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in‐depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune‐mediated treatments, and introduces the burgeoning domain of antibody–drug conjugates, bispecific antibodies, and multitarget‐directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations. Potential strategies and potential targets for treating EC. Current the EC's research focuses on pivotal genes EGFR, HER2, TP53, CDKN2A, and APC, targeting key pathways in cell regulation and signaling. We highlight four novel therapeutic strategies: combined targeted therapy with chemotherapy, radiotherapy, immunotherapy, and multitarget approaches. Mechanistic insights into esophageal carcinogenesis underscore alterations in EGFR/ErbB, PI3K/AKT/mTOR, and Notch/Wnt/β‐catenin pathways, driving proliferative and survival signaling cascades. CDKN2A, cyclin‐dependent kinase inhibitor 2A; EC, esophageal cancer; EGFR, endothelial growth factor receptor; HER2, human epidermal growth factor receptor 2; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3‐kinase; TP53, tumor protein 53.

Combined modality treatment with chemotherapy, radiotherapy, and immunotherapy is a crucial therapeutic approach for lung cancer. However, controversies still exist regarding radiation doses, treatment regimens, and the risk of pneumonitis. This study aimed to conduct a comprehensive meta-analysis and in-depth subgroup analyses based on randomized controlled trials (RCTs) involving lung cancer patients undergoing radiotherapy to assess whether its combination with immunotherapy is effective and safe. We systematically searched PubMed, Cochrane Central, Embase, and major conferences for randomized trials evaluating immune checkpoint inhibitors (ICIs) plus radiotherapy in lung cancer. The outcomes included progression-free survival (PFS), overall survival (OS), and the incidence of adverse reactions, particularly focusing on pneumonitis/pneumonia. Subgroup analyses were performed based on radiotherapy modalities, the timing of ICIs treatment, tumor stage, pathological type, and types of ICIs. Fifteen trials were included in this analysis. The addition of ICIs to radiotherapy or chemoradiotherapy significantly improved PFS (HR = 0.76, 95% CI 0.70-0.83) and OS (HR = 0.83, 95% CI 0.75-0.92). In subgroup analyses, stereotactic body radiotherapy (SBRT) (HR = 0.38, 95% CI 0.19-0.75) and hypo-fractionated radiotherapy (Hypo-RT) (HR = 0.49, 95% CI 0.31-0.79) were associated with improved PFS. Consolidation ICIs treatment improved OS (HR = 0.68, 95% CI 0.59-0.79), while concurrent ICIs had no significant effect (HR = 1.06, 95% CI 0.87-1.28). In terms of tumor stage, Stage I NSCLC patients (HR = 0.38, 95% CI 0.19-0.75) showed significant PFS improvement with ICIs. Both PD-1 (HR = 0.39, 95% CI 0.22-0.69) and PD-L1 (HR = 0.75, 95% CI 0.64-0.87) inhibitors were linked to improved PFS in irradiated lung cancer patients, and PD-L1 also enhanced OS (HR = 0.82, 95% CI 0.68-0.99). The addition of ICIs increased the risk of any-grade pneumonitis/pneumonia (RR = 1.27, 95% CI 1.12-1.44) but did not elevate the risk of severe (grade ≥3) events (RR = 1.12, 95% CI 0.78-1.60). Notably, among patients treated with SBRT, no significant increase was observed in the incidence of pneumonitis of any grade. PD-1/PD-L1 inhibitors combined with radiotherapy especially SBRT can enhance survival outcomes in lung cancer without increasing the risk of severe pneumonitis/pneumonia, supporting their clinically manageable safety profile. https://www.crd.york.ac.uk/PROSPERO/home, identifier CRD420251140111.