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Abstract Heat stress (HS) poses a significant challenge to plant survival, necessitating sophisticated molecular mechanisms to maintain cellular homeostasis. Here, we identify SICKLE (SIC) as a key modulator of HS responses in Arabidopsis (Arabidopsis thaliana). SIC is required for the sequestration of RNA DEBRANCHING ENZYME 1 (DBR1), a rate-limiting enzyme of lariat intronic RNA (lariRNA) decay, into stress granules (SGs). The sequestration of DBR1 by SIC enhances the accumulation of lariRNAs, branched circular RNAs derived from excised introns during pre-mRNA splicing, which in turn promote the transcription of their parental genes. Our findings further demonstrate that SIC-mediated DBR1 sequestration in SGs is crucial for plant HS tolerance, as deletion of the N-terminus of SIC (SIC1–244) impairs DBR1 sequestration and compromises plant response to HS. Overall, our study unveils a mechanism of transcriptional regulation in the HS response, where lariRNAs are enriched through DBR1 sequestration, ultimately promoting the transcription of heat stress tolerance genes.

In view of the lack of knowledge concerning the evolution, hotspots, and frontiers of energy research in the hospitality industry, this paper explores the development of energy research and knowledge in the hospitality industry by conducting information mining and knowledge mapping using bibliometric analysis of publications obtained from the Web of Science. Our findings demonstrate that (1) interdisciplinary research combining natural science and social science is essential for advancing the field of hotel energy consumption. (2) The knowledge base shifted from engineering and architecture to hotel management and social science, with early hotspots including building refrigeration systems and thermal storage devices, while the energy-saving behavior of stakeholders is a new frontier. (3) Since 2006, hotspots have shifted from energy performance and accounting to energy consumption benchmark formulation, carbon emission accounting, and customer green behavior, indicating high integration and future research trends. The results of this study provide a fundamental framework for researchers to investigate energy-related aspects in the hospitality industry. Our findings demonstrate the need for interdisciplinary research, highlighting that hotel management must integrate natural and social sciences to develop effective energy-saving strategies, reduce energy consumption, and minimize carbon emissions.

AbstractObjective This study aims to explore the correlation between central and peripheral thyroid resistance indices and diabetic retinopathy(DR) in patients with type 2 diabetes mellitus (T2DM), so as to provide a clinical basis for the prevention and treatment of diabetic retinopathy.Methods This study retrospectively analyzed 1249 euthyroid patients with T2DM hospitalized in the Department of Endocrinology, Peking University International Hospital from January 2017 to June 2022, including 852 males and 397 females, with an average age of 54.73 ± 13.40 years. According to the degree of DR, the patients were divided into three groups including the no diabetic retinopathy (NDR) group, non-proliferative diabetic retinopathy (NPDR) group and proliferative diabetic retinopathy (PDR) group.Results Free thymidine (FT4), thyroid stimulating hormone (TSH), thyroid feedback quantile index (TFQI), thyrotropin-T4 resistance index (TT4RI), thyroid stimulating hormone index (TSHI) and free triiodothyronine/free thyroxine (FT3/FT4) levels among the three groups were significantly different, with the NDR group having lowest TSH, TFQI, TT4QI, TSHI and the highest in the PDR group (all p

Background: According to the 2023 guidelines for treating non-small-cell lung cancer (NSCLC), first-line treatment and recently developed agents for the treatment of epidermal growth factor (EGFR) mutation-positive locally advanced or metastatic NSCLC were compared in this meta-analysis. Treatment regimens involved in the included studies included first, second, and third-generation tyrosine kinase inhibitors (TKIs), TKIs plus chemotherapy, TKIs plus angiogenesis inhibitors, and platinum-containing doublet chemotherapy with or without bevacizumab. Considering the varying efficacy and safety of drugs in people of different ethnic origins, the optimal regimen should be determined, and the safety of first-line treatments should be assessed in the Asian population specifically.Methods: PubMed, Embase, the Cochrane Library, Web of Science, and the China National Knowledge Infrastructure (CNKI) were systematically searched to retrieve reports on randomized controlled trials (RCTs) with research data published from inception to 1 February 2023. Adopting Asian patient populations as the target (including studies in which Asian patients accounted for more than 50% of the sample), a network meta-analysis (NMA) was conducted for comparison of treatment regimens and treatments were ranked based on the surface under the cumulative ranking curve (SUCRA).Results: A total of 19 RCTs involving 5,824 patients and covering 14 treatment regimens were included. The primary outcome measure examined in this study was progression-free survival (PFS); other outcome measures examined were overall survival (OS), disease control rate (DCR), objective response rate (ORR), occurrence of any adverse events (AE), occurrence of adverse events of grade 3 or above (≥3AE), and occurrence of serious adverse events (SAE). In terms of PFS, all regimens including TKIs (as a monotherapy or in combination with other therapies), as well as bevacizumab (Bev) plus chemotherapy (Ch) were found to be significantly superior to basic chemotherapy (HRs: 0.09–0.61, p < 0.05 in all cases compared with Ch alone). The highest-ranking therapies were erlotinib (Erl) plus Bev (SUCRA: 0.94) and Erl plus ramucirumab (Ram) (SUCRA: 0.93). Regarding OS, no significant differences was observed between first-line treatment strategies; the top four treatments based on SUCRA, in rank order, were Bev + Ch (0.87), gefitinib (Gef) plus Ch (0.81), dacomitinib (Dac) (0.79), and osimertinib (Osi) (0.69). Additionally, there were no significant differences between first-line treatment strategies in terms of DCR. Regarding ORR, the top three treatments based on SUCRA were Erl + Bev (0.85), Erl + Ram (0.76), and Gef + Ch (0.74). No significant difference between first-line treatment strategies was observed in terms of the risk of AE. However, based on SUCRA, Erl ranked highest on avoidance of ≥ 3AE (0.97), and Osi ranked highest on avoidance of SAE (0.91).Conclusion: Based on these analyses of survival benefits, tumor burden response, and safety, furmonertinib (Fur), Osi, and aumolertinib (Aum) may represent the best treatment regimen options for Asian patients, significantly prolonging survival (as measured by median PFS/OS), eliciting a greater tumor burden response, and exposing patients to a lower risk of adverse events. Although Erl + Bev and Erl + Ram are associated with the best survival benefits in terms of PFS, further clinical studies are still needed to identify ways to reduce the risk of adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42023407994, identifier CRD42023407994

Analyzing collaborations on energy research in the hotel industry has important implications for promoting the research performance in this field. The Web of Science Core Collection from 1984 to 2022 was used to analyze the research contributions and cooperation networks and clusters at three levels: macro (national level), meso (institutional level), and micro (key authors and papers) using a bibliometric approach. The results show the following. (1) The cooperative relationship is the closest between China and the United States. Developed countries in Europe exhibit more academic cooperation. (2) There is a significant regional imbalance in the cooperation between universities. Leading universities rely on their strengths in energy research or hotel management and are often highly productive institutions. (3) The breadth of the authors' cooperation is insufficient. Collaborative research dominated by productive authors tends to focus on practical issues in the local hotel industry. The collaboration between experts from different disciplines benefits from the complementary advantages of these experts. (4) Hotel energy research has evolved from single-disciplinary research in the early days to interdisciplinary research in recent years. This paper provides visualizations of current conditions and deficiencies in existing research collaborations and provides a reference for analyzing the potential of research cooperation.

Many techniques have been developed for extracting DNA, but most are often complex, time-consuming, and/or expensive. In this study, we describe a simple, rapid and cost-effective technique for preparing DNA template for PCR. This technique involves 0.1 M potassium hydroxide treatment at 100°C for 10 min followed by centrifugation. The suspended centrifuged sediments were shown as excellent templates for PCR. Templates prepared using this technique worked for diverse microorganisms belonging to bacteria, fungi and oomycetes and their amplification efficiencies were comparable to/better than those prepared using common but relatively more complex, time-consuming, and/or expensive methods, including commercial DNA extraction kits. Furthermore, this technology is suitable for high-throughput batch processing and for amplifications of long DNA fragments. Flow cytometry and scanning electronic microscopy analyzes showed that this technique generated primarily damaged cells and cell-bound DNA, not free naked DNA. This technique provides a great convenience for simple PCR template preparation.

Plant hormone brassinosteroids (BRs) play key roles in plant adaptation to biotic stresses, including various pathogen infections. As a core factor in BR signaling, the transcription factor BRI1-EMS-SUPPRESSOR 1 (BES1) activates BR responses via regulating the expression of target genes. However, the molecular mechanism of BRs in regulating plant immunity is unclear, and the key components are not identified. In this study, we found that BR biosynthesis and signaling transduction are essential for plant resistance to pathogen infection, and BR biosynthesis or BR signaling-deficient mutants displayed susceptibility to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) infection [including more serious symptoms and more photosystem II (PSII) photochemistry damage]. We identified a callose synthase gene GLUCAN SYNTHASE-LIKE 8 (GSL8) as a direct target of BES1, and its expression was induced by BRs/BES1. Meanwhile, BRs induced callose accumulation after Pst DC3000 infection. Moreover, BES1 gain-of-function mutant bes1-D showed promoted Pst DC3000 resistance. GSL8 T-DNA insertion mutant gsl8-1 was susceptible to DC3000, while brassinolide (BL) treatment partially rescued gsl8-1 susceptible phenotypes. Our study suggests that BR-induced pathogen resistance partly depends on the BR-induced BES1-GSL8 cascade to mediate callose accumulation.

In higher plants, chloroplasts are essential semi-autonomous organelles with complex compartments. As part of these sub-organellar compartments, the sheet-like thylakoid membranes contain abundant light-absorbing chlorophylls bound to the light-harvesting proteins and to some of the reaction center proteins. About half of the thylakoid membrane proteins are encoded by nuclear genes and synthesized in the cytosol as precursors before being imported into the chloroplast. After translocation across the chloroplast envelope by the Toc/Tic system, these proteins are subsequently inserted into or translocated across the thylakoid membranes through distinct pathways. The other half of thylakoid proteins are encoded by the chloroplast genome, synthesized in the stroma and integrated into the thylakoid through a cotranslational process. Much progress has been made in identification and functional characterization of new factors involved in protein targeting into the thylakoids, and new insights into this process have been gained. In this review, we introduce the distinct transport systems mediating the translocation of substrate proteins from chloroplast stroma to the thylakoid membrane, and present the recent advances in the identification of novel components mediating these pathways. Finally, we raise some unanswered questions involved in the targeting of chloroplast proteins into the thylakoid membrane, along with perspectives for future research.

Engineered biological nanopores enable observation of single molecule chemistry events; however a cylindrical pore geometry can have undesired effects. The authors report a conical biological pore which was embedded with tetrachloroaurate(III) to allow for discrimination between different biothiols.

In higher plants, chloroplasts are vital organelles possessing highly complex compartmentalization. As most chloroplast-located proteins are encoded in the nucleus and synthesized in the cytosol, the correct sorting of these proteins to appropriate compartments is critical for the proper functions of chloroplasts as well as plant survival. Nuclear-encoded chloroplast proteins are imported into stroma and further sorted to distinct compartments via different pathways. The proteins predicted to be sorted to the thylakoid lumen by the chloroplast twin arginine transport (cpTAT) pathway are shown to be facilitated by STT1/2 driven liquid-liquid phase separation (LLPS). Liquid-liquid phase separation is a novel mechanism to facilitate the formation of membrane-less sub-cellular compartments and accelerate biochemical reactions temporally and spatially. In this review, we introduce the sorting mechanisms within chloroplasts, and briefly summarize the properties and significance of LLPS, with an emphasis on the novel function of LLPS in the sorting of cpTAT substrate proteins. We conclude with perspectives for the future research on chloroplast protein sorting and targeting mechanisms.

Neuropathic pain is a complex disease with high incidence. Adenosine triphosphate (ATP) and its activated P2X7 receptor are involved in the signal transmission of neuropathic pain. Gallic acid (3,4,5-trihydroxybenzoic acid) is a traditional Chinese medicine obtained from natural plants that exhibit anti-inflammatory, analgesic, and antitumor effects. However, the underlying mechanism for gallic acid in analgesia remains unknown. This study aims to reveal how gallic acid alleviates neuropathic pain behaviors in a rat model with chronic constriction injury (CCI). Real-time PCR, western blotting, double-label immunofluorescence, molecular docking, and whole-cell patch clamp technology were used to explore the therapeutic action of gallic acid on neuropathic pain. The results showed that after CCI rats were treated with gallic acid for 1 week, the mechanical withdrawal threshold and thermal withdrawal latency were increased, accompanied by inhibition of the upregulated expression of P2X7 and TNF-α at both mRNA and protein levels, and reduced NF-κB and phosphorylated-STAT3 in the dorsal root ganglia. At the same time, gallic acid significantly decreased the coexpression of P2X7 and glial fibrillary acidic protein in the dorsal root ganglia. In addition, gallic acid could suppress ATP-activated current in human embryonic kidney 293 (HEK293) cells transfected with the plasmid expressing P2X7 but had no effect on ATP activation current of P2X7-mutant plasmid (with the point mutation sequence of the key site where gallic acid binds to the P2X7 receptor). Therefore, our work suggests that gallic acid may alleviate neuropathic pain in CCI rats by inhibiting the P2X7 receptor and subsequent activation of the TNF-α/STAT3 signaling pathway.

Human immunodeficiency virus envelope glycoprotein 120 (gp120) leads to hyperalgesia. Long non-coding RNAs are characterized by the lack of a protein-coding sequence and may contribute to the development and maintenance of inflammatory and neuroinflammatory pain. Rats with neuroinflammatory pain were established by gp120 treatment, which is featured by intensified pain behaviors. Long non-coding RNA uc.48+ was increased in the dorsal root ganglia of gp120-treated rats, and small interfering RNA that targets uc.48+ markedly alleviated hyperalgesia in gp120-treated rats. Notably, uc.48+ overexpression increased P2Y12 expression in control rats dorsal root ganglia and induced hyperalgesia. Uc.48+ small interfering RNA inhibited P2Y12 expression in gp120-treated rats. Uc.48+ potentiated P2Y12 receptor functions in the neurons and heterologous cells. Therefore, uc.48+ siRNA treatment reduced the upregulation of P2Y12 expression and function in DRG neurons, and, hence, alleviated hyperalgesia in gp120-treated rats.

The celiac ganglion projects its postganglionic (including purinergic) fibers to the liver. P2Y12 receptor is one of the P2Y family members. We found that the expression levels of P2Y12 receptor in both celiac ganglia and liver were increased in type 2 diabetes mellitus (T2DM) rats which also displayed an enhanced activity of celiac sympathetic nerve discharge (SND). In addition, a marked decrease of hepatic glucokinase (GK) expression was accompanied by reduced hepatic glycogen synthesis in T2DM rats, whereas meanwhile the levels of NLRP3, active caspase-1, NF-κB, and interleukin-1β were elevated. All these abnormal alterations could be largely reversed after treatment of short hairpin RNA (shRNA) targeting P2Y12. Our results indicate that the silence of P2Y12 by shRNA may effectively correct the anomalous activity of celiac SND and improve the dysfunctional hepatic glucokinase by counteracting hepatocyte inflammation and likely pyroptosis due to activated NLRP3 inflammasome and caspase-1 signaling, thereby attenuating hyperglycemia in T2DM rats.

Retrograde signalling co-ordinates nuclear gene expression in response to stress perceived in the chloroplast. Here Guo et al. show that a MAPK cascade acting downstream of a plastid derived Ca2+signal contributes to the regulation of nuclear gene expression by phosphorylation of ABI4 during retrograde signalling.

This work reported a highly sensitive ethanol sensor assembled from raspberry-like hierarchical Ce-doped WO _3 nanoparticles. The Ce-doped WO _3 nanoparticles doped with different contents (0, 2, 4 and 8 at%) of Ce were synthesized by a facile hydrothermal method. The crystalline structure and the micromorphology of Ce-doped WO _3 nanoparticles were measured by x-ray diffraction (XRD) and field-emission scanning electron microscopy (FESEM), respectively. The x-ray photoelectric spectroscopy (XPS) and transmission electron microscopy (TEM) attached with energy-dispersive spectroscopy (EDS) confirmed the elemental distribution and the chemical state of surface elements. Comparison between the pristine and Ce-doped WO _3 samples revealed that the doping of Ce on WO _3 can powerfully improve the response ability to ethanol. As the doping content of Ce element was 4 at%, the sensor exhibited optimal response to ethanol in the range of 0.1–50 ppm at the working temperature of 350 °C. The response can achieve a high value of 12.3 for detecting 1 ppm ethanol with a fast response/recovery (6s/6s). Impressively, the sensor still maintained a good response (8.1) to ethanol even at sub-ppm level (0.1 ppm ethanol). This work will pave a platform for design and development of highly sensitive ethanol sensors.

The hydrangea macrophylla -like SnO _2 microspheres doped with different Ce contents (0, 2, 6 and 10 mol%) were synthesized by a facile hydrothermal method. The crystal phase, micro morphology and element composites were investigated by x-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) with energy-dispersive spectroscopy (EDS) and x-ray photoelectric spectroscopy (XPS). The results demonstrated the hydrangea macrophylla -like microstructure of the prepared samples and the existence of Ce ^3+ /Ce ^4+ when doped with Ce element. Furthermore, the synthesized Ce-doped SnO _2 samples’ sensing properties were investigated. The SnO _2 microspheres doped with 6 mol% showed the largest response to acetone during 0.2–20 ppm at 320 °C as well as good selectivity and reproducibility. As discussed, the Ce doping that generates n-n type heterojunction and the Ce ^3+ /Ce ^4+ conversion increases the resistance change of Ce-doped SnO _2 in reducing atmosphere and enhances the response.

Nanostructured surfaces can be engineered to kill bacteria in a contact-dependent manner. The study of bacterial interactions with a nanoscale topology is thus crucial to developing antibacterial surfaces. Here, a systematic study of the effects of nanoscale topology on bactericidal activity is presented. We describe the antibacterial properties of highly ordered and uniformly arrayed cotton swab-shaped (or mushroom-shaped) nanopillars. These nanostructured surfaces show bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa. A biophysical model of the cell envelope in contact with the surface, developed ab initio from the infinitesimal strain theory, suggests that bacterial adhesion and subsequent lysis are highly influenced by the bending rigidity of the cell envelope and the surface topography formed by the nanopillars. We used the biophysical model to analyse the influence of the nanopillar cap geometry on the bactericidal activity and made several geometrical alterations of the nanostructured surface. Measurement of the bactericidal activities of these surfaces confirms model predictions, highlights the non-trivial role of cell envelope bending rigidity, and sheds light on the effects of nanopillar cap architecture on the interactions with the bacterial envelope. More importantly, our results show that the surface nanotopology can be rationally designed to enhance the bactericidal efficiency.

Two new dibenzocyclooctadiene lignans, neglschisandrins C-D (1-2), were isolated from the stems of Schisandra neglecta. Their structures and stereochemistries were elucidated by spectroscopic methods, including 1D- and 2D-NMR and HR-ESI-MS techniques.

Two new dibenzocyclooctene lignans, neglschisandrins A-B (1-2), were isolatedfrom the stems of Schisandra neglecta. Their structures and stereochemistries wereelucidated by spectroscopic methods, including 1D- and 2D-NMR and HR-ESI-MStechniques.

Stroke is the second-leading cause of death and the leading cause of disability in much of the world. In particular, China faces the greatest challenge from stroke, since the population is aged quickly. In decades of clinical trials, no neuroprotectant has had reproducible efficacy on primary clinical end points, because reperfusion is probably a necessity for neuroprotection to be clinically beneficial. Fortunately, the success of thrombolysis and endovascular thrombectomy has taken us into a reperfusion era of acute ischaemic stroke (AIS) therapy. Brain cytoprotective agents can prevent detrimental effects of ischaemia, and therefore ‘freeze’ ischaemic penumbra before reperfusion, extend the time window for reperfusion therapy. Because reperfusion often leads to reperfusion injury, including haemorrhagic transformation, brain oedema, infarct progression and neurological worsening, cytoprotective agents will enhance the efficacy and safety of reperfusion therapy by preventing or reducing reperfusion injuries. Therefore, reperfusion and cytoprotective agents are a mutually beneficial pair in AIS therapy. In this review, we outline critical pathophysiological events causing cell death within the penumbra after ischaemia or ischaemia/reperfusion in the acute phase of AIS, focusing on excitotoxicity and free radicals. We discuss key pharmacological targets for cytoprotective therapy and evaluate the recent advances of cytoprotective agents going through clinical trials, highlighting multitarget cytoprotective agents that intervene at multiple levels of the ischaemic and reperfusion cascade.