Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Ecofriendly Controlled-Release Insecticide Carrier: pH-/Temperature-Responsive Rosin-Derived Hydrogels for Avermectin Delivery against Mythimna separata (Walker).

The exploration of environmentally friendly, less toxic, sustained-release insecticide is increasing with the growing demand for food to meet the requirements of the expanding population. As a sustained-release carrier, the unique, environmentally friendly intelligent responsive hydrogel system is an important factor in improving the efficiency of insecticide utilization and accurate release. In this study, we developed a facile approach for incorporating the natural compound rosin (dehydroabietic acid, DA) and zinc ions (Zn2+) into a poly(N-isopropylacrylamide) (PNIPAM) hydrogel network to construct a controlled-release hydrogel carrier (DA-PNIPAM-Zn2+). Then, the model insecticide avermectin (AVM) was encapsulated in the carrier at a drug loading rate of 36.32% to form AVM@DA-PNIPAM-Zn2+. Surprisingly, the smart controlled carrier exhibited environmental responsiveness, strongly enhanced mechanical properties, self-healing ability, hydrophobicity, and photostability to ensure a balance between environmental friendliness and the precision of the drug release. The release experiments showed that the carboxyl and amide groups in the polymer chains alter the intermolecular forces within the hydrogel meshes and ingredient diffusion by changing temperatures (25 and 40 °C) and pH values (5.8, 7.4, and 8.5), leading to different release behaviors. The insecticidal activity of the AVM@DA-PNIPAM-Zn2+ against oriental armyworms was good, with an effective minimum toxicity toward aquatic animals. Therefore, AVM@DA-PNIPAM-Zn2+ is an effective drug delivery system against oriental armyworms. We anticipate that this ecofriendly, sustainable, smart-response carrier may broaden the utilization rosin and its possible applications in the agricultural sector.

Effects of acupuncture on sleep quality in patients with Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the evidence relating to acupuncture on the sleep quality of patients with Parkinson's disease. DATA SOURCES: Six English-language (PubMed, Cochrane Library, EBSCOhost, Embase, OVID MEDLINE, and Web of Science) and four Chinese-language (China National Knowledge Infrastructure, SinoMed, China Scientific Journals Database, and Wanfang) databases were searched for pertinent studies published from database inception to 11 October 2023. METHODS: Two researchers independently screened eligible studies and extracted relevant data using custom data extraction tables. Methodological quality assessment of the included studies was performed using Cochrane Handbook 5.1.0. Meta-analysis was performed using Cochrane Review Manager version 5.4. RESULTS: Twenty-four studies (1701 participants) met inclusion criteria. The meta-analysis showed that acupuncture improved the Parkinson's Disease Sleep Scale, Pittsburgh Sleep Quality Index, Hamilton Anxiety Scale, Hamilton Depression Scale, Self-Rating Depression Scale, and Parkinson's Disease Questionnaire 39 scores compared with controls (all P < 0.05). CONCLUSION: This review showed that acupuncture improved sleep quality, anxiety and depressive symptoms, and quality of life of patients with Parkinson's disease relative to controls.

Tissue-resident innate lymphoid cells in asthma.

Asthma is a chronic airway inflammatory disease whose global incidence increases annually. The role of innate lymphoid cells (ILCs) is a crucial aspect of asthma research with respect to different endotypes of asthma. Based on its pathological and inflammatory features, asthma is divided into type 2 high and type 2 low endotypes. Type-2 high asthma is distinguished by the activation of type 2 immune cells, including T helper 2 (Th2) cells and ILC2s; the production of cytokines interleukin (IL)-4, IL-5 and IL-13; eosinophilic aggregation; and bronchial hyper-responsiveness. Type-2 low asthma represents a variety of endotypes other than type 2 high endotype such as the IL-1ß/ILC3/neutrophil endotype and a paucigranulocytic asthma, which may be insensitive to corticosteroid treatment and/or associated with obesity. The complexity of asthma is due to the involvement of multiple cell types, including tissue-resident ILCs and other innate immune cells including bronchial epithelial cells, dendritic cells, macrophages and eosinophils, which provide immediate defence against viruses, pathogens and allergens. On this basis, innate immune cells and adaptive immune cells combine to induce the pathological condition of asthma. In addition, the plasticity of ILCs increases the heterogeneity of asthma. This review focuses on the phenotypes of tissue-resident ILCs and their roles in the different endotypes of asthma, as well as the mechanisms of tissue-resident ILCs and other immune cells. Based on the phenotypes, roles and mechanisms of immune cells, the therapeutic strategies for asthma are reviewed.

Potential-Resolved Electrochemiluminescence Multiplex Immunoassay for Florfenicol and Chloramphenicol in a Single Sample.

The simultaneous detection of multiple antibiotic residues in food is of great significance for food safety. In this work, a novel dual-potential electrochemiluminescence (ECL) immunoassay was designed for the simultaneous detection of chloramphenicol and fluorfenicol residues in food. Ru@MOF was used as an anodic probe, and SnS2 QDs-PEI-Au-MoS2 was used as a cathodic probe. Notably, the coreactant for both luminophores was K2S2O8, avoiding interactions caused by different kinds of coreactants. Au nanoparticles functionalized with a nitrogen- and sulfur-doped graphene oxide-modified glassy carbon electrode to improve the electron transfer efficiency and provide a larger surface area for immobilization of antigen. The linear range for the detection of florfenicol was determined to be 0.1-1000 ng mL-1 with a detection limit of 0.03 ng mL-1, and the linear range for the detection of chloramphenicol was 0.01-1000 ng mL-1 with a detection limit of 3.2 pg mL-1 by recording the ECL responses at two different excitation potentials. The proposed immunoassay achieved a more stable recovery in the detection of actual samples and provided a new analytical method for the simultaneous detection of florfenicol and chloramphenicol residues with high sensitivity and specificity.

Palmitoylation landscapes across human cancers reveal a role of palmitoylation in tumorigenesis.

BACKGROUND: Protein palmitoylation, which is catalyzed by palmitoyl-transferase and de-palmitoyl-transferase, plays a crucial role in various biological processes. However, the landscape and dynamics of protein palmitoylation in human cancers are not well understood. METHODS: We utilized 23 palmitoyl-acyltransferases and seven de-palmitoyl-acyltransferases as palmitoylation-related genes for protein palmitoylation analysis. Multiple publicly available datasets were employed to conduct pan-cancer analysis, examining the transcriptome, genomic alterations, clinical outcomes, and correlation with c-Myc (Myc) for palmitoylation-related genes. Real-time quantitative PCR and immunoblotting were performed to assess the expression of palmitoylation-related genes and global protein palmitoylation levels in cancer cells treated with Myc depletion or small molecule inhibitors. Protein docking and drug sensitivity analyses were employed to predict small molecules that target palmitoylation-related genes. RESULTS: We identified associations between palmitoylation and cancer subtype, stage, and patient survival. We discovered that abnormal DNA methylation and oncogenic Myc-driven transcriptional regulation synergistically contribute to the dysregulation of palmitoylation-related genes. This dysregulation of palmitoylation was closely correlated with immune infiltration in the tumor microenvironment and the response to immunotherapy. Importantly, dysregulated palmitoylation was found to modulate canonical cancer-related pathways, thus influencing tumorigenesis. To support our findings, we performed a proof-of-concept experiment showing that depletion of Myc led to reduced expression of most palmitoylation-related genes, resulting in decreased global protein palmitoylation levels. Through mass spectrometry and enrichment analyses, we also identified palmitoyl-acyltransferases ZDHHC7 and ZDHHC23 as significant contributors to mTOR signaling, DNA repair, and immune pathways, highlighting their potential roles in tumorigenesis. Additionally, our study explored the potential of three small molecular (BI-2531, etoposide, and piperlongumine) to modulate palmitoylation by targeting the expression or activity of palmitoylation-related genes or enzymes. CONCLUSIONS: Overall, our findings underscore the critical role of dysregulated palmitoylation in tumorigenesis and the response to immunotherapy, mediated through classical cancer-related pathways and immune cell infiltration. Additionally, we propose that the aforementioned three small molecule hold promise as potential therapeutics for modulating palmitoylation, thereby offering novel avenues for cancer therapy.

Classification models for predicting the bioactivity of pan-TRK inhibitors and SAR analysis.

Tropomyosin receptor kinases (TRKs) are important broad-spectrum anticancer targets. The oncogenic rearrangement of the NTRK gene disrupts the extracellular structural domain and epitopes for therapeutic antibodies, making small-molecule inhibitors essential for treating NTRK fusion-driven tumors. In this work, several algorithms were used to construct descriptor-based and nondescriptor-based models, and the models were evaluated by outer 10-fold cross-validation. To find a model with good generalization ability, the dataset was partitioned by random and cluster-splitting methods to construct in- and cross-domain models, respectively. Among the 48 models built, the model with the combination of the deep neural network (DNN) algorithm and extended connectivity fingerprints 4 (ECFP4) descriptors achieved excellent performance in both dataset divisions. The results indicate that the DNN algorithm has a strong generalization prediction ability, and the richness of features plays a vital role in predicting unknown spatial molecules. Additionally, we combined the clustering results and decision tree models of fingerprint descriptors to perform structure-activity relationship analysis. It was found that nitrogen-containing aromatic heterocyclic and benzo heterocyclic structures play a crucial role in enhancing the activity of TRK inhibitors. Workflow for generating predictive models for TRK inhibitors.

CYP311A1 in the anterior midgut is involved in lipid distribution and microvillus integrity in Drosophila melanogaster.

Lipids are either taken up from food sources or produced internally in specialized tissues such as the liver. Among others, both routes of lipid metabolism involve cytochrome P450 monooxygenases (CYPs). We sought to analyze the function of Cyp311a1 that has been shown to be expressed in the midgut of the fruit fly Drosophila melanogaster. Using a GFP-tagged version of CYP311A1 that is expressed under the control of its endogenous promoter, we show that Cyp311a1 localizes to the endoplasmic reticulum in epithelial cells of the anterior midgut. In larvae with reduced Cyp311a1 expression in the anterior midgut, compared to control larvae, the apical plasma membrane of the respective epithelial cells contains less and shorter microvilli. In addition, we observed reduction of neutral lipids in the fat body, the insect liver, and decreased phosphatidylethanolamine (PE) and triacylglycerols (TAG) amounts in the whole body of these larvae. Probably as a consequence, they cease to grow and eventually die. The microvillus defects in larvae with reduced Cyp311a1 expression are restored by supplying PE, a major phospholipid of plasma membranes, to the food. Moreover, the growth arrest phenotype of these larvae is partially rescued. Together, these results suggest that the anterior midgut is an import hub in lipid distribution and that the midgut-specific CYP311A1 contributes to this function by participating in shaping microvilli in a PE-dependent manner.

Effects of acupuncture on obstructive sleep apnea-hypopnea syndrome: A meta-analysis.

Our study aimed to systematically evaluate the effect of acupuncture in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Literature search of four Chinese databases and six English databases for studies published from the inception of each database to March 1, 2022 and identify relevant studies published in Chinese or English. Related randomized controlled trials of acupuncture for the treatment of OSAHS were included to analyze the efficacy of acupuncture. Two researchers independently reviewed all of the retrieved studies to screen for eligible studies and extract the required relevant data. Included studies were subjected to a methodological quality assessment using the Cochrane Manual 5.1.0, and to a meta-analysis using Cochrane Review Manager version 5.4. A total of 19 studies with 1365 participants were examined. Compared with the control group, the apnea-hypopnea index, lowest oxygen saturation, Epworth Sleepiness Scale, interleukin-6, tumor necrosis factor α, and nuclear factor κ-B indicators all exhibited statistically significant changes. Thus, acupuncture was effective in alleviating the state of hypoxia and sleepiness and reduced the inflammatory response and disease severity among reported patients with OSAHS. Therefore, acupuncture could be widely used in the clinical treatment of OSAHS patients as a complementary strategy and warrants further study.

Evaluation of dressings preventing facial medical device-related pressure injury in medical staff during the COVID-19 pandemic: A systematic review and network meta-analysis.

AIM: This study systematically compared the efficacy of various dressings that may prevent facial medical device-related pressure injury (MRDPI) in medical staff during the COVID-19 pandemic. BACKGROUND: During the COVID-19 pandemic, medical staff who are required to wear masks, goggles and other personal protective equipment (PPE) are susceptible to facial MRDPI, which exacerbates working conditions. Dressings can effectively prevent or alleviate MRDPI, but it is unclear which dressings are most effective. DESIGN: A systematic review and network meta-analysis, in accordance with PRISMA. METHODS: A comprehensive literature search was conducted in four English and four Chinese databases to identify relevant studies published up to 8 September 2022. The selected studies were randomised controlled trials, with populations comprising medical staff who wore PPE during the COVID-19 pandemic and included an observation and control group. RESULTS: The network meta-analysis of the 12 selected articles showed that foam dressing, hydrocolloid dressing and petrolatum gauze were better than conventional protection for preventing MRDPI. The surface under the cumulative ranking curve indicated that foam dressing was the best preventative. CONCLUSION: Foam dressing is more effective than other dressings in preventing facial MRDPI in medical staff. When PPE must be worn for many hours, such as during the COVID-19 pandemic, medical staff can use foam dressings to prevent MRDPI. RELEVANCE TO CLINICAL PRACTICE: The results support the use of dressings, especially foam dressings, to prevent MRDPI in healthcare workers. The appropriate dressings are recommended to prevent MRDPI associated with wearing PPE.

Incidence of facial pressure injuries in health-care professionals during the COVID-19 pandemic: A systematic review and meta-analysis.

AIM: To evaluate the incidence of facial pressure injuries in health-care professionals during the COVID-19 pandemic in a meta-analysis. METHODS: Related studies were obtained through electronic databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI) Chinese Scientific Journal (VIP) China Biomedical Literature service systems (CBM) and Wanfang Data (from inception to 27 November 2021). The pooled incidence and the 95% confidence interval of facial pressure injuries were calculated with Review Manager v5.4 software. RESULTS: Overall, 16 studies with 14 430 health-care professionals were included. Pooled results showed that the pooled incidence of facial pressure injury in health-care professionals was 58.8% (95% CI: 49.0%-68.7%; p < 0.01). The results of the subgroup analysis showed that the incidence of facial pressure injury in these staff was high, and predominantly stage I pressure injury, in the following cases: in health-care professionals who wore personal protective equipment for longer than 4 h, in those without any training experience, and on the nose. CONCLUSION: Administrators and researchers should pay attention to preventing facial pressure injury related to the wearing of personal protective equipment (PPE) by ensuring all health-care professionals receive training and by limiting prolonged periods of use.

Influencing factors of medical device-related pressure ulcers in medical personnel during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVE: To determine the influencing factors of medical device related pressure injury (MDRPU) in medical staff by meta-analysis. METHODS: A comprehensive literature search was conducted by PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, CBM, and WanFang Data (from inception to July 27, 2022). Two researchers independently performed literature screening, quality evaluation and data extraction, and meta-analysis was conducted with RevMan 5.4 and Stata12.0 software. RESULTS: Total of 11215 medical staff were included in 9 articles. Meta analysis showed that gender, occupation, sweating, wearing time, single working time, department of COVID-19, preventive measures, and level 3 PPE were the risk factors for MDRPU in medical staff (P < 0.05). CONCLUSION: The outbreak of COVID-19 led to the occurrence of MDRPU among medical staff, and the influencing factors should be focused on. The medical administrator can further improve and standardize the preventive measures of MDRPU according to the influencing factors. Medical staff should accurately identify high-risk factors in the clinical work process, implement intervention measures, and reduce the incidence of MDRPU.

Discovery of Novel Epidermal Growth Factor Receptor (EGFR) Inhibitors Using Computational Approaches.

The epidermal growth factor receptor (EGFR) signaling pathway plays an important role in cell growth, proliferation, differentiation, and other physiological processes, which makes the EGFR a promising target for anticancer therapies. The discovery of novel EGFR inhibitors may provide a solution to the problem of drug resistance. In this work, we performed a ligand-based virtual screening (LBVS) protocol for finding novel EGFR inhibitors from a 5.3 million compound library. First, the 3D shape-based similarity was used to obtain structurally novel EGFR inhibitors. In this study, we tried three queries; two were crystal structures and one was generated from deep generative models of graphs (DGMG). Next, we have built four structure-activity relationship (SAR) models and three quantitative structure-activity relationship (QSAR) models based on an SVM method for further screening of highly active EGFR inhibitors. Experimental validations led to the identification of nine hits out of 18 tested compounds. Among them, hit 1, hit 5, and hit 6 had IC50 values around 80 nM against EGFR whose interactions with EGFR were further investigated by molecular dynamics simulations.

Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing.

Precise regulation of embryonic neurodevelopment is crucial for proper structural organization and functioning of the adult brain. The key molecular machinery orchestrating this process remains unclear. Anaplastic lymphoma kinase (ALK) is an oncogenic receptor-type protein tyrosine kinase that is specifically and transiently expressed in developing nervous system. However, its role in the mammalian brain development is unknown. We found that transient embryonic ALK inactivation caused long-lasting abnormalities in the adult mouse brain, including impaired neuronal connectivity and cognition, along with delayed neuronal migration and decreased neuronal proliferation during neurodevelopment. scRNA-seq on human cerebral organoids revealed a delayed transition of cell-type composition. Molecular characterization identified a group of differentially expressed genes (DEGs) that were temporally regulated by ALK at distinct developmental stages. In addition to oncogenes, many DEGs found by scRNA-seq are associated with neurological or neuropsychiatric disorders. Our study demonstrates a pivotal role of oncogenic ALK pathway in neurodevelopment and characterized cell-type-specific transcriptome regulated by ALK for better understanding mammalian cortical development.

Petroleum spill bioremediation by an indigenous constructed bacterial consortium in marine environments.

In the process of marine oil spill remediation, adding highly efficient oil degrading microorganisms can effectively promote oil degradation. However, in practice, the effect is far less than expected due to the inadaptability of microorganisms to the environment and their disadvantage in the competition with indigenous bacteria for nutrients. In this article, four strains of oil degrading bacteria were isolated from seawater in Jiaozhou Bay, China, where a crude oil pipeline explosion occurred seven years ago. Results of high-throughput sequencing, diesel degradation tests and surface activity tests indicated that Peseudomonas aeruginosa ZS1 was a highly efficient petroleum degrading bacterium with the ability to produce surface active substances. A diesel oil-degrading bacterial consortium (named SA) was constructed by ZS1 and another oil degrading bacteria by diesel degradation test. Degradation products analysis indicated that SA has a good ability to degrade short chain alkanes, especially n-alkanes (C10-C18). Community structure analysis showed that OTUs of Alcanivorax, Peseudomona, Ruegeria, Pseudophaeobacter, Hyphomonas and Thalassospira on genus level increased after the oil spill and remained stable throughout the recovery period. Most of these enriched microorganisms were related to known alkane and hydrocarbon degraders by the previous study. However, it is the first time to report that Pseudophaeobacter was enriched by using diesel as the sole carbon source. The results also indicated that ZS1 may have a dominant position in competition with indigenous bacteria. Oil pollution has an obvious selective effect on marine microorganisms. Although the oil degradation was promoted after SA injection, the recovery of microbial community structure took a longer time.

Frontline nurses' willingness to work during the COVID-19 pandemic: A mixed-methods study.

AIM: Frontline nurses' willingness to work has significant implications for maintaining workforce stability and quality of care during the COVID-19 pandemic; however, few studies have investigated their willingness and the corresponding reasons. This study aims to examine frontline nurses' willingness to work, identify its predictors and explore its corresponding reasons. DESIGN: A mixed-methods design was conducted. METHODS: Based on a multilevel behavioural-diagnostic model, a questionnaire survey was used to collect quantitative and qualitative data concurrently from 13 February to 24 February 2020 to explore frontline nurses' willingness to work and the corresponding reasons in two hospitals in Wuhan, China. One was a designated hospital which only received COVID-19 patients, and the other was built up temporarily for COVID-19 patients. RESULTS: Of the 2014 participants, most (n = 1950, 96.8%) indicated their willingness to work, and a few (n = 64, 3.2%) expressed their unwillingness. Binary logistic regression analysis identified five predictors of participants' willingness to work, including monthly family income, average working hours per shift, belief in their colleagues' preparedness, belief in their hospitals' preparedness and levels of depression. These indicators explained 27% of the variance (p < .05). Frontline nurses' willingness to work mainly arose from professional commitment, patriotism and faith, while unwillingness to do so primarily stemmed from safety concerns and family responsibility. CONCLUSION: Most frontline nurses were willing to work and showed great professional commitment. IMPACT: Professional commitment and patriotism were two important individual-level factors affecting frontline nurses' willingness to work during a pandemic. Strategies should be implemented, such as appreciating and acknowledging their contribution, rewarding their valuable work, arranging reasonable working hours, enhancing colleagues' and hospitals' preparedness, and providing emotional support. Moreover, adequate personal protective equipment, self-protection training and social support should be ensured to address frontline nurses' safety concerns and family responsibility.

Final report of a prospective randomized study on thoracic radiotherapy target volume for limited-stage small cell lung cancer with radiation dosimetric analyses.

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

Expression of sirtuins in ovarian follicles of postnatal mice.

Mammalian ovarian follicular development is an intricate, elaborate, and well-organized phenomenon regulated by various signaling pathways; however, the underlying mechanism remains unclear. Mammalian sirtuins (sirtuin 1 to sirtuin 7) are a group of NAD+ -dependent deacetylases implicated in various physiological processes including cell proliferation, apoptosis, cell cycle progression, and insulin signaling. Mammalian ovarian sirtuins have been studied using adult and aged bovine, porcine, and murine models. However, limited information is available regarding their precise expression patterns and the localization of follicle development in mice. This study aimed to assess the dynamic expression and localization of all seven sirtuins in early postnatal mouse ovaries through real-time polymerase chain reaction analysis and immunohistochemistry, respectively. During postnatal ovarian follicle development, sirtuin 1, sirtuin 4, and sirtuin 6 were downregulated compared with those in 1-day postnatal mouse ovaries (p < .05), indicating that these three sirtuin genes may be markers of follicular development. Combining their localization in granulosa cells through immunohistochemical studies, sirtuin 1, sirtuin 4, and sirtuin 6 are suggested to play negative regulatory roles in mammal ovarian follicular granulosa cell development. Furthermore, we found that sirtuin 2 (p < .05) and sirtuin 7 (p < .05) mRNA were constantly upregulated relative to sirtuin 1, although limited information is available regarding sirtuin 7. Among all sirtuins in mouse ovaries, sirtuin 1 was relatively and steadily downregulated. Upon sirtuin 1 overexpression in 1-day postnatal mouse ovaries via sirtuin 1-harboring adenoviruses in vitro, the emergence of primary follicles was delayed, as was the emergence of secondary follicles in 4-day postnatal ovaries. Further studies on KGN cell lines reported that interfering with sirtuin 1 expression in granulosa cell significantly affected granulosa cell proliferation and the expression of mitochondrial genes. This study presents the first systemic analysis of dynamic patterns of sirtuin family expression in early postnatal mice ovaries, laying the foundation for further studies on less discussed sirtuin subtypes, such as sirtuin 5 and sirtuin 7.

Transcriptional profiling of long noncoding RNAs and their target transcripts in ovarian cortical tissues from women with normal menstrual cycles and primary ovarian insufficiency.

Previous studies have shown that long noncoding RNAs (lncRNAs) show a highly tissue- and disease-specific expression pattern and that they regulate the expression of neighboring genes. Because lncRNAs have been shown to be secreted into the general circulation, they may be used as diagnostic tools for some diseases. Primary ovarian insufficiency (POI) is a disease in which women have menstrual cessation before the age of 40, accompanied by elevated follicle stimulating hormone and decreased estrogen levels. In this study, ovarian cortical tissues from five women with normal menstrual cycles and from five POI patients were used for next-generation RNA sequencing. We found 20 differentially expressed lncRNAs with 12 upregulated and eight downregulated lncRNAs in cortical tissues of POI ovaries, compared with normal controls (fold change ≥ 2 and false discovery rate[FDR] ≤ 0.05). We also found 52 differentially expressed messenger RNA transcripts, with 33 upregulated and 19 downregulated ones (foldchange ≥ 2 and FDR ≤ 0.05). Functional annotation showed that these differentially expressed transcripts were associated with follicular development and granulosa cell function. Thirteen differentially expressed lncRNAs and their targeted neighboring transcripts were coregulated in ovarian cortical tissues, including lnc-ADAMTS1-1:1/ADAMTS1, lnc-PHLDA3-3:2/CSRP1, lnc-COL1A1-5:1/COL1A1, lnc-SAMD14-5:3/COL1A1, and lnc-GULP1-2:1/COL3A1. Furthermore, serum levels of these lncRNAs in POI patients were significantly different from those in normal patients ( p < 0.05), and expression differences were consistent with those in ovarian cortical tissues. This study showed that key lncRNAs were differentially expressed in both ovarian cortical tissues and serum samples between women with normal menstrual cycles and POI patients. Further studies on the regulation of ovarian lncRNAs during follicular development are critical in understanding the etiologies of POI. Analyses of lncRNA expression in serum samples might provide a basis for early diagnosis and treatment of POI.

Reconfigurable RGB dye lasers based on the laminar flow control in an optofluidic chip.

The optofluidic dye laser serves as an important on-chip optical source in microfluidic technology for a breadth of applications. One of the ultimate goals of such a light source is an optofluidic white dye laser. However, realizing such a device has been challenging, because it is difficult to achieve simultaneous multi-wavelength lasers that span the most visible spectrum, especially on an integrated system. Here, we demonstrate white lasing in an optofluidic chip that simultaneously lases in red, green, and blue (RGB) colors inside a microfluidic channel. A Fabry-Perot cavity formed by two end-coated fibers provides the optical feedback of the laser. Easy reconfigurable emission can be obtained based on the laminar flow control. Eventually, white lasing at a low threshold was obtained when the pumping energy density is in excess of 26.1 µJ/mm2.