Proteomic Stratification of Prognosis and Treatment Options for Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models. Here, we analyzed formalin-fixed, paraffin-embedded (FFPE) samples of surgical resections by proteomic profiling, and stratified SCLC into three proteomic subtypes (S-I, S-II, and S-III) with distinct clinical outcomes and chemotherapy responses. The proteomic subtyping was an independent prognostic factor and performed better than current tumor-node-metastasis or Veterans Administration Lung Study Group staging methods. The subtyping results could be further validated using FFPE biopsy samples from an independent cohort, extending the analysis to both surgical and biopsy samples. The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy. Differentially overexpressed proteins in S-III, the worst prognostic subtype, allowed us to nominate potential therapeutic targets, indicating that patient selection may bring new hope for previously failed clinical trials. Finally, analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy. Collectively, our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.

Construction and application of procedural pathways combined with information management in nursing staff skills training system.

OBJECTIVE: To explore the application effect of procedural pathways combined with information management in the construction of nursing staff skills training system. METHODS: This was a quasi-experimental study with a control group and an experimental group. A total of 300 newly admitted nurses or nurses who required training within three years of admission were selected as the experimental group, and 267 nurses who were trained in the same hospital during the same period in 2020 were selected as the control group. The experimental group received skills training using a system that combines procedural pathways with information management, while the control group received traditional teaching mode. The outcome measures included theoretical score, operation score, nurse competency, patient satisfaction, and nursing-related adverse events. The data were analyzed using t-test, chi-square test, and rank-sum test. RESULTS: The experimental group had higher scores in theoretical assessment, skills assessment, nurse competency, and patient satisfaction, and lower incidence of nursing-related adverse events than the control group (P < 0.05). CONCLUSION: The strategy of procedural pathways combined with information management provides a new perspective and method for nursing operation skills training, effectively improves clinical nursing quality and ensures patient safety.

Porphyrin(2.1.2.1) organopalladium complexes as efficient singlet oxygen sensitizers.

Four new non-planar and non-aromatic porphyrin organopalladium complexes were synthesized. Conformational structures and optical and electronic properties of the obtained organopalladium complexes containing meso-substituted phenyl, p-tert-butylphenyl, or pentafluorophenyl groups were fully investigated. These complexes showed potent capacity for singlet oxygen (1O2) generation under blue-light irradiation, and the 1O2 quantum yields were in the range of 41%-56%, which were comparable to that of Ru(bpy)3Cl2 (57%), and such potency made these organopalladium complexes potential 1O2 photo sensitizers for photodynamic therapy.

Stabilization of the Neutral [25]Hexaphyrin(1.0.1.0.1.0) Radical by Hetero-Bimetal-Coordination.

Stabilization of hexaphyrin(1.0.1.0.1.0) (named "rosarin") in its 25π radical state is achieved using a hetero-bimetal-coordination strategy. The antiaromatic BF2 complex B-1 was first synthesized, and then rhodium ion was inserted into B-1 to produce the BF2/Rh(CO)2 mixed complex Rh-B-1 as a highly air-stable radical. The structures of B-1 and Rh-B-1 were determined by single-crystal X-ray diffractions, and the antiaromatic or radical character was identified by various spectroscopy evidence and theoretical calculations. Rh-B-1 exhibits excellent redox properties, enabling amphoteric aromatic-antiaromatic conversion to their 24/26π states. Compared to the 24/26π conjugation systems on the same skeleton, Rh-B-1 has the narrowest electrochemical and optical band gaps, with the longest absorption band at 1010 nm. The ring-current analysis reveals intense paratropic currents for B-1 and co-existing diatropic-paratropic currents for Rh-B-1. This hetero-bimetal-coordination system provides a novel platform for organic radical stabilization on porphyrinoids, showing the prospect of modulating ligand oxidation states through rational coordination design.

Electrocatalytic Oxygen Reduction Reaction of Peripheral Functionalized Cobalt Porphyrins(2.1.2.1).

Two peripheral functionalized clamp-shaped cobalt porphyrin(2.1.2.1) complexes were synthesized, and their electrocatalytic ORR abilities were investigated. The crystal data and optical and redox properties of them were revised by peripheral modification. The ORR capacities and DFT calculations of F5PhCo and F5NCo suggest superior selectivity for the 4e- ORR pathway. This work further confirms the clamp-shaped cobalt porphyrin complexes are ideal Co-N4 ORR catalysts.

Covid-19 psychological pressures, depression and FOMO: the mediating role of online social support and emotional regulation.

BACKGROUND: The spread of the coronavirus has led to significant anxiety among university students, resulting in various mental health problems that could potentially impact their academic performance. METHOD: To examine the mediating role of emotional regulation and online social support in the relationships between COVID-19 psychological pressures, depression, and the fear of missing out (FoMO) among young adult university students, a cross-sectional research design was employed using an online survey. The sample consisted of 521 full-time university students from China, currently enrolled in undergraduate and postgraduate programs. RESULTS: Findings revealed that more than half (55.09%, n=287) of the university students experienced COVID-19 psychological pressures. These pressures directly contributed to increased levels of depression (ß = 0.339, p < .001) and fear of missing out (ß = 0.236, p < .001). Moreover, online social support and emotional regulation exhibited partial mediating effects on the association between COVID-19 psychological pressures, depression, and the fear of missing out. The results indicated that COVID-19 psychological pressures were linked to higher levels of depressive symptoms and a greater fear of missing out among university students. CONCLUSIONS: However, the provision of timely and adequate online social support, as well as the implementation of emotional regulation strategies, mitigated the negative effects of the pandemic on students' social and emotional well-being. Consequently, this led to reduced levels of depression and fear of missing out.

Benzene-fused porphyrin(2.1.2.1) array: synthesis, structure, and electrocatalytic hydrogen evolution.

The development of efficient molecular catalysts for the electrocatalytic hydrogen evolution reaction (HER) is very necessary and important for fuel cells. In this work, we report a new benzene-fused porphyrin(2.1.2.1) array, BPD, with a unique S-shaped molecular conformation. The electrochemistry of BPD displays multielectron donating and accepting properties owing to the two porphyrin(2.1.2.1) blocks and degenerate molecular orbitals. The electrocatalytic HER activity of BPD is remarkably higher-that is, BPD exhibited lower overpotential, faster HER kinetics, faster charge transfer kinetics, and extended catalytic stability-than that of the porphyrin(2.1.2.1) copper complex monomer.

Synthesis of Hybrid Porphyrin(2.1.2.1)s and Their Complexation.

Novel hybrid porphyrin(2.1.2.1)s and their boron and copper complexes were synthesized using the "toy bricks" synthetic method. Crystal data, frontier molecular orbital calculations, and electrostatic potential surface maps reveal that hybridization in the porphyrin(2.1.2.1) donor-acceptor unit controls the selective coordination of BF2.

Distribution and Antimicrobial Resistance Characterization of Listeria monocytogenes in Poultry Meat in Jiading District, Shanghai.

To investigate the distribution, contamination status, and antibiotic resistance of Listeria monocytogenes in four types of retail poultry meat, including chicken, duck, goose, and pigeon, sold in Jiading District, Shanghai, a total of 236 retail poultry meat samples were collected, and L. monocytogenes isolates were obtained for identification and antibiotic susceptibility testing against 14 common antibiotics. Forty-one L. monocytogenes isolates were detected from the 236 retail poultry meat samples, with detection rates of 24.47%, 19.44%, 14.75%, and 4.44% in chicken, goose, duck, and pigeon meat, respectively. Among refrigerated, frozen, and room temperature samples, refrigerated poultry had the highest detection rate at 25.40%, while frozen poultry had the lowest at 13.33%. The detection rate of L. monocytogenes in chicken meat differed significantly between the storage temperatures, while no significant differences were found for other poultry types. No significant differences in detection rates were observed between different retail locations or packaging methods. Isolates exhibited complete resistance to cefoxitin (FOX) and increasing resistance over time to tetracycline (TET) and clindamycin (CLI), while low levels of resistance were found for penicillin (PEN), oxacillin (OXA), and erythromycin (ERY). Resistance to ERY and TET suggests the potential for multidrug resistance. Significant differences in antibiotic resistance profiles were observed among L. monocytogenes from the various poultry types. In summary, contamination status and antibiotic resistance profiles differed among retail chicken, duck, goose, and pigeon meat sold and the resistance rate of strains continues to increase in Jiading District, Shanghai. Targeted control measures should be implemented to reduce the emergence of resistant strains, as retail conditions had minimal impact on L. monocytogenes prevalence in poultry meat.

Effect of NaOH Pretreatment on Permeability and Surface Properties of Three Wood Species.

To improve the permeability of wood, three chemical reagents were used to pretreat Chinese fir, white oak, and poplar. Through a factorial experiment with the mass change rate of the wood as the indicator, NaOH was preliminarily selected as the pretreatment agent. Further orthogonal experiments were conducted to explore the effects of NaOH concentration, temperature, and treatment time on the mass change rate, dye uptake rate, transverse dye penetration rate, and color difference of the wood. A fuzzy, comprehensive analysis was used to optimize the pretreatment process. The results showed that after NaOH pretreatment, the highest mass change rates of Chinese fir, white oak, and poplar were 11.30, 10.66, and 8.53%, respectively. Compared with untreated wood, the dye uptake rate of three wood species increased by 1.05, 1.43, and 1.13 times, respectively; the radial dye penetration rate increased by 5.05, 4.14, and 3.38 times, respectively; and the tangential dye penetration rate increased by 3.91, 3.45, and 3.84 times, respectively. These findings indicate an enhancement in permeability for all three wood species following NaOH pretreatment. The brightness of the three wood species decreased after NaOH pretreatment, while the yellow and red colors increased in Chinese fir and poplar and decreased in white oak. Scanning electron microscopy showed that pits in the wood opened after pretreatment, while extractives decreased. Infrared spectroscopy analysis indicated varying degrees of extraction effects from NaOH pretreatment across the three wood species, along with increased active hydroxyl groups within the wood structure. X-ray diffraction analysis revealed that NaOH dissolved noncrystalline substances in wood, leading to improved crystallinity. These experimental findings provide essential data for future endeavors in wood pretreatment and subsequent staining processes.

ATR inhibition induces synthetic lethality in mismatch repair-deficient cells and augments immunotherapy.

The mismatch repair (MMR) deficiency of cancer cells drives mutagenesis and offers a useful biomarker for immunotherapy. However, many MMR-deficient (MMR-d) tumors do not respond to immunotherapy, highlighting the need for alternative approaches to target MMR-d cancer cells. Here, we show that inhibition of the ATR kinase preferentially kills MMR-d cancer cells. Mechanistically, ATR inhibitor (ATRi) imposes synthetic lethality on MMR-d cells by inducing DNA damage in a replication- and MUS81 nuclease-dependent manner. The DNA damage induced by ATRi is colocalized with both MSH2 and PCNA, suggesting that it arises from DNA structures recognized by MMR proteins during replication. In syngeneic mouse models, ATRi effectively reduces the growth of MMR-d tumors. Interestingly, the antitumor effects of ATRi are partially due to CD8+ T cells. In MMR-d cells, ATRi stimulates the accumulation of nascent DNA fragments in the cytoplasm, activating the cGAS-mediated interferon response. The combination of ATRi and anti-PD-1 antibody reduces the growth of MMR-d tumors more efficiently than ATRi or anti-PD-1 alone, showing the ability of ATRi to augment the immunotherapy of MMR-d tumors. Thus, ATRi selectively targets MMR-d tumor cells by inducing synthetic lethality and enhancing antitumor immunity, providing a promising strategy to complement and augment MMR deficiency-guided immunotherapy.

Rapid multi-task diagnosis of oral cancer leveraging fiber-optic Raman spectroscopy and deep learning algorithms.

Introduction: Oral cancer, a predominant malignancy in developing nations, represents a global health challenge with a five-year survival rate below 50%. Nonetheless, substantial reductions in both its incidence and mortality rates can be achieved through early detection and appropriate treatment. Crucial to these treatment plans and prognosis predictions is the identification of the pathological type of oral cancer. Methods: Toward this end, fiber-optic Raman spectroscopy emerges as an effective tool. This study combines Raman spectroscopy technology with deep learning algorithms to develop a portable intelligent prototype for oral case analysis. We propose, for the first time, a multi-task network (MTN) Raman spectroscopy classification model that utilizes a shared backbone network to simultaneously achieve different clinical staging and histological grading diagnoses. Results: The developed model demonstrated accuracy rates of 94.88%, 94.57%, and 94.34% for tumor staging, lymph node staging, and histological grading, respectively. Its sensitivity, specificity, and accuracy compare closely with the gold standard: routine histopathological examination. Discussion: Thus, this prototype proposed in this study has great potential for rapid, non-invasive, and label-free pathological diagnosis of oral cancer.

Ovarian toxicity of e-cigarette liquids: Effects of components and high and low nicotine concentration e-cigarette liquid in vitro.

INTRODUCTION: Electronic cigarette use has become increasingly popular, with potential consequences for reproductive health. We aimed to investigate the effects of different components of e-liquid on the ovary and compare the impact of low nicotine concentration e-liquids (LN e-liquids) and high nicotine concentration e-liquids (HN e-liquids) on ovarian toxicity. METHODS: A total of 378 rat ovaries were divided into seven groups, including control (no intervention), nicotine (0.05 mg/mL), flavoring (0.25 µL/mL), propylene glycol (PG) (2.5 µL/mL), vegetable glycerin (VG) (2.0 µL/mL), LN e-liquid (0.05 mg nicotine + 0.25 µL flavoring + 2.5 µL PG + 2.0 µL VG + 0.25 µL distilled water/mL medium) and HN e-liquid groups (0.05 mg nicotine + 0.05 µL flavoring + 0.5 µL PG + 0.4 µL VG + 0.05 µL distilled water/mL medium). After three hours of in vitro culture, ovarian morphology, oxidation levels [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA)], and apoptosis levels [factor related apoptosis (Fas), Cyt-c, Caspase-9, Caspase-3] were analyzed. RESULTS: Our findings indicate that nicotine has limited impact on the ovary, while flavoring, PG, and VG all cause ovarian damage including morphological damage, disruption of oxidative balance and promotion of apoptosis, with VG having the most significant effect. Moreover, LN e-liquids may lead to more severe ovarian damage than HN e-liquids at an equal intake of total nicotine. CONCLUSIONS: Our study highlights that in e-liquid formula, nicotine has a limited effect on the ovaries, but flavoring, PG, and VG all cause damage to the ovaries, with VG the most damaging. At a consistent level of total nicotine intake, e-liquids with low nicotine concentrations cause more damage to the ovaries than those with high nicotine concentrations. These findings contribute to a better understanding of the impact of e-liquids on ovarian health and have important implications for public health policy.

Corrigendum: A genome-wide investigation of effects of aberrant DNA methylation on the usage of alternative promoters in hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fonc.2021.780266.].

A solar/radiative cooling dual-regulation smart window based on shape-morphing kirigami structures.

The energy efficiency of buildings has become a critical issue due to their substantial contribution to global energy consumption. Windows, in particular, are often the least efficient component of the building envelope, and conventional smart windows focus solely on regulating solar transmittance while overlooking radiative cooling. Although several recent designs achieved dual-control of solar and radiative cooling, these windows still face limitations in terms of durability, limited modulation ability and energy-saving performance. To address these challenges, we propose a novel dual-control smart window design consisting of a reconfigurable kirigami structure and polydimethylsiloxane-laminated thermochromic hydrogel coated with silver nanowires. In summer, the thermochromic hydrogel turns translucent to suppress the solar heat gain, while the high emissivity kirigami structure covers the exterior surface of the window, promoting radiative cooling. In winter, the hydrogel becomes transparent to allow for solar transmission. Additionally, the kirigami structure undergoes an out-of-plane structural change, opening towards the outside environment to expose the underlying low-emissivity silver nanowires and suppress heat radiation. Our design achieves a promising solar transmittance modulation ability of ∼24% and a good long-wave infrared emissivity regulation ability of 0.5. Furthermore, it exhibits significantly improved durability, which is nine times longer than the lifespan of conventional smart hydrogels. Our novel approach offers a promising solution for constructing energy-efficient and durable smart windows and outperforms existing state-of-the-art solar/radiative cooling dual-regulation smart windows in the literature.

The microglial innate immune receptors TREM-1 and TREM-2 in the anterior cingulate cortex (ACC) drive visceral hypersensitivity and depressive-like behaviors following DSS-induced colitis.

Inflammatory bowel disease (IBD) is a chronic condition with a high recurrence rate. To date, the clinical treatment of IBD mainly focuses on inflammation and gastrointestinal symptoms while ignoring the accompanying visceral pain, anxiety, depression, and other emotional symptoms. Evidence is accumulating that bi-directional communication between the gut and the brain is indispensable in the pathophysiology of IBD and its comorbidities. Increasing efforts have been focused on elucidating the central immune mechanisms in visceral hypersensitivity and depression following colitis. The triggering receptors expressed on myeloid cells-1/2 (TREM-1/2) are newly identified receptors that can be expressed on microglia. In particular, TREM-1 acts as an immune and inflammatory response amplifier, while TREM-2 may function as a molecule with a putative antagonist role to TREM-1. In the present study, using the dextran sulfate sodium (DSS)-induced colitis model, we found that peripheral inflammation induced microglial and glutamatergic neuronal activation in the anterior cingulate cortex (ACC). Microglial ablation mitigated visceral hypersensitivity in the inflammation phase rather than in the remission phase, subsequently preventing the emergence of depressive-like behaviors in the remission phase. Moreover, a further mechanistic study revealed that overexpression of TREM-1 and TREM-2 remarkably aggravated DSS-induced neuropathology. The improved outcome was achieved by modifying the balance of TREM-1 and TREM-2 via genetic and pharmacological means. Specifically, a deficiency of TREM-1 attenuated visceral hyperpathia in the inflammatory phase, and a TREM-2 deficiency improved depression-like symptoms in the remission phase. Taken together, our findings provide insights into mechanism-based therapy for inflammatory disorders and establish that microglial innate immune receptors TREM-1 and TREM-2 may represent a therapeutic target for the treatment of pain and psychological comorbidities associated with chronic inflammatory diseases by modulating neuroinflammatory responses.

Climate Change, Extreme Temperatures and Sex-Related Responses in Spiders.

Climatic extremes, such as heat waves, are increasing in frequency, intensity and duration under anthropogenic climate change. These extreme events pose a great threat to many organisms, and especially ectotherms, which are susceptible to high temperatures. In nature, many ectotherms, such as insects, may seek cooler microclimates and 'ride out´ extreme temperatures, especially when these are transient and unpredictable. However, some ectotherms, such as web-building spiders, may be more prone to heat-related mortality than more motile organisms. Adult females in many spider families are sedentary and build webs in micro-habitats where they spend their entire lives. Under extreme heat, they may be limited in their ability to move vertically or horizontally to find cooler microhabitats. Males, on the other hand, are often nomadic, have broader spatial distributions, and thus might be better able to escape exposure to heat. However, life-history traits in spiders such as the relative body size of males and females and spatial ecology also vary across different taxonomic groups based on their phylogeny. This may make different species or families more or less susceptible to heat waves and exposure to very high temperatures. Selection to extreme temperatures may drive adaptive responses in female physiology, morphology or web site selection in species that build small or exposed webs. Male spiders may be better able to avoid heat-related stress than females by seeking refuge under objects such as bark or rocks with cooler microclimates. Here, we discuss these aspects in detail and propose research focusing on male and female spider behavior and reproduction across different taxa exposed to temperature extremes.

Research trends of acupuncture therapy for hypertension over the past two decades: a bibliometric analysis.

Acupuncture has already been extensively utilized to treat high blood pressure (hypertension) in several nations. Nevertheless, the bibliometric research on the worldwide usage of acupuncture for hypertension is mostly unclear. As a result, our objective for the research aimed to investigate the present state as well as developments in the global usage of acupuncture on hypertension during the last 20 years using CiteSpace (5.8.R2). The Web of Science (WOS) database examined papers on acupuncture treatment of hypertension from 2002 to 2021. We examined the number of publications, cited journals, nations/regions, organizations, authors, cited authors, cited references, and keywords utilizing CiteSpace. The record of 296 documents was obtained between 2002 and 2021. The quantity and frequency of annual publications rose gradually. Regarding frequency and centrality of citations, Circulation and Clin Exp Hypertens (Clinical and Experimental Hypertension) scored top and second respectively. China had the most publications among countries/regions, as well as the five largest institutions were also in China. Cunzhi Liu was the most productive author, while P Li was the most referenced author. XF Zhao produced the first article inside the quantity of cited references classification. 'Electroacupuncture' had a significant frequency with centrality for the keywords, which suggested electroacupuncture is a popular treatment in this field. In the treatment of hypertension, electroacupuncture has a beneficial effect on reducing blood pressure. However, because of the many different applications of electroacupuncture frequencies in research, whether the electroacupuncture frequency is connected to the therapeutic impact should be given more significant consideration. The findings of this bibliometric analysis give an overview of the present state as well as developments of clinical studies on acupuncture for hypertensive patients during the last two decades, which could assist researchers in identifying hot subjects and exploring novel directions in further study within the field.

Effect and mechanism of acupuncture on Alzheimer's disease: A review.

With the development trend of an aging society, Alzheimer's disease (AD) has become an urgent problem in the field of medicine worldwide. Cognitive impairment in AD patients leads to a decline in the ability to perform daily living and abnormalities in behavior and personality, causing abnormal psychiatric symptoms, which seriously affect the daily life of patients. Currently, mainly drug therapy is used for AD patients in the clinic, but a large proportion of patients will experience drug efficacy not working, and even some drugs bring severe sleep disorders. Acupuncture, with its unique concept and treatment method, has been validated through a large number of experiments and proved its reliability of acupuncture in the treatment of AD. Many advances have been made in the study of the neurobiological mechanisms of acupuncture in the treatment of AD, further demonstrating the good efficacy and unique advantages of acupuncture in the treatment of AD. This review first summarizes the pathogenesis of AD and then illustrates the research progress of acupuncture in the treatment of AD, which includes the effect of acupuncture on the changes of biochemical indicators in AD in vivo and the specific mechanism of action to exert the therapeutic effect. Changes in relevant indicators of AD similarly further validate the effectiveness of acupuncture treatment. The clinical and mechanistic studies of acupuncture in the treatment of AD are intensified to fit the need for social development. It is believed that acupuncture will achieve new achievements in the treatment of AD as research progresses.

The circadian regulation of extracellular ATP.

Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the nervous system and immune system by activating P2 purinergic receptors. Recent increasingly studies showed that extracellular ATP exhibits circadian oscillation with an approximately 24-h periodicity, which participates in regulatory pathways of central oscillator suprachiasmatic nucleus and peripheral oscillator bladder, respectively. Oscillators modulate the protein expression of ATP release channels and ectonucleotidase activity through clock genes; indeed, real-time alterations of ATP release and degradation determine outcomes of temporal character on extracellular ATP rhythm. The regulatory pathways on extracellular ATP rhythm are different in central and peripheral systems. In this review, we summarize the circadian rhythm of extracellular ATP and discuss several circadian regulatory pathways in different organs via ATP release and degradation, to provide a new understanding for purinergic signaling in the regulatory mechanism of circadian rhythm and a potential target to research the circadian regulation of extracellular ATP in other circadian oscillators.