Epidemic trend, genetic characteristics, and transmission networks of HIV-1 among treatment-naive men who have sex with men in Hebei province, China.

Introduction: Homosexual transmission has contributed greatly to the current HIV-1 epidemic in Hebei province, China. Dolutegravir (DTG) will be conditionally used as a component of free antiretroviral therapy (ART) according to manual for national free anti-AIDS treatment drugs (2023 edition) issued by China in June 2023. However, current genetic characteristics and pretreatment drug resistance (PDR) to proteinase inhibitors (PIs), reverse transcriptase inhibitors (RTs) and integrase strand transfer inhibitors (INSTIs) of HIV-1 in this population have remained unclear. Methods: Serial consecutive cross-sectional analyses for HIV- 1 infection trend, genetic characteristics, PDR and molecular transmission networks were conducted from 2018 to 2022. All of participants were HIV-1- infected MSM newly diagnosed at the HIV surveillance points (HSPs) in Hebei, China. Evidence of PDR was confirmed using the world health organization (WHO) list for surveillance of drug resistance mutations. Results: In this study, a total of 14 HIV-1 subtypes were circulating in the HSPs of Hebei province, China. CRF01_ AE (51.9%, 350/675), CRF07_BC (30.4%, 205/675), B (6.2%, 42/675) and URFs (5.8%, 39/675) were the four most predominant subtypes among MSM. And, CRF07_BC (r > 0) and URFs (r > 0) indicated an increasing trend, respectively; however, CRF01_AE (r < 0) showed a decline trend. The overall prevalence of HIV-1 PDR showed a substantial increase from 6.3% in 2018 to 7.9% in 2022. The prevalence of NNRTI-PDR was the highest (5.8%, 39/675), followed by INSTIs (2.4%, 16/675), NRTIs (0.6%, 4/675) and PIs (0.3%, 2/675). Furthermore, extensive HIV-1 strains bearing PDR were circulating in the MSM population via molecular transmission networks for major HIV-1 subtypes, especially CRF01_AE and CRF07_BC. Discussion: Our findings reflect that HIV-1 epidemic in the MSM population is complex and severe in Hebei, China. Therefore, it is urgent for us to implement more effective intervention measures to limit the further dissemination of HIV-1, especially the spread of HIV-1 INSTI-PDR strains.

Construction of a diagnostic model for ischemic stroke based on immune-related genes.

INTRODUCTION: This study aimed to screen immune-related marker genes of ischemic stroke (IS). MATERIAL AND METHODS: Two IS-related gene expression datasets were downloaded. The significantly differentially expressed genes (DEGs) and miRNAs (DEMs) between IS and control groups were selected. The differential immune cells were analysed. Weighted gene co-expression network analysis (WGCNA) was applied to analyse immune-related genes, followed by function analysis and interaction network construction. Then, key genes were further screened using optimization algorithm to construct a diagnostic model. Finally, miRNA regulatory network of several key genes was established. RESULTS: In total 321 DEGs and 140 DEMs were obtained. 11 immune cell types were significantly different between IS and control groups. WGCNA identified two key modules, involving 202 differential immune genes. The greenyellow module was enriched in biological processes and pathways associated with T cells, while the midnightblue module was mainly associated with apoptosis, and inflammatory response-related functions and pathways. Protein interaction network identified 10 hub nodes, such as CD8A, ITGAM and TLR4. LASSO regression selected 8 key feature genes, and a risk score model was established. Key model genes were enriched in 63 GO biological processes, such as microglial cell activation, and B cell apoptotic process, and 3 KEGG pathways, such as negative regulation of nuclear cell cycle DNA replication, and hematopoietic cell lineage. Finally, a total of 25 miRNA-target relationship pairs were obtained. CONCLUSIONS: This study identified some immune-related marker genes and constructed a diagnostic model based on 8 immune-related genes in IS.

Variation of nitrate sources affected by precipitation with different intensities in groundwater in the piedmont plain area of alluvial-pluvial fan.

A substantial reservoir of nitrogen (N) in soil poses a threat to the quality and safety of shallow groundwater, especially under extreme precipitation that hastens nitrogen leaching into groundwater. However, the specific impact of varying precipitation intensities on the concentration and sources of nitrate (NO3-) in groundwater across diverse hydrogeological zones and land uses remains unclear. This study aims to elucidate the fluctuations in NO3- concentration, sources, and controlling factors in shallow groundwater under different intensities of precipitation (extreme heavy precipitation and continuous heavy precipitation) in a typical alluvial-pluvial fan of the North China Plain by using stable isotopes (δ2H-H2O, δ18O-H2O, δ15N-NO3-, δ18O-NO3-), hydrochemical analyses and the SIAR model. Affected by extreme heavy precipitation the depleted isotopes of δ2H-H2O and δ18O-H2O in groundwater of the entire area suggested the rapid recharge of fast flow by precipitation. The enriched isotopes of δ2H-H2O and δ18O-H2O of north part in alluvial fan after continuous heavy precipitation showed the recharge of translatory flow of soil water. NO3-concentrations increased to 78.9 mg/L after extreme heavy precipitation and increased to 105.3 mg/L after continuous heavy precipitation when compared to those in normal year (56.8 mg/L) of north part of the alluvial fan. However, NO3- concentrations had slight variation after continuous heavy precipitation of south part of the fan due to the deep vadose zone. The contribution ratio of sources of NO3- in groundwater by using SIAR analysis revealed manure & sewage (MS) as the primary NO3- source (accounting for 59.7-78.1%) before extreme heavy precipitation, chemical fertilizer (CF) making a minor contribution (6.9-17.3%). Different precipitation events and land use types lead to changes in NO3- sources. Affected by extreme heavy precipitation, the contribution of MS decreased while CF increased, particularly in vegetables (26.2-28.1%) and farmland (29.2-34.7%). After continuous heavy precipitation, MS increased again, particularly in vegetables (50.0%) and farmlands (20.4-66.4%), with CF either increasing or remaining steady. This indicated that continuous heavy precipitation accelerated the leaching of nitrogen (organic manure application) stored in deep soil to groundwater and it has a larger influence on the increasing of NO3- concentrations of groundwater than extreme heavy precipitation which carried nitrogen (chemical fertilizer application) in shallow soil to groundwater by fast flow. These findings underscore the importance of considering soil chemical N stores and their implications for groundwater contamination mitigation under future extreme climate scenarios, particularly in agricultural management practices.

The impact of social network embeddedness, TPB, and danwei system on residents' participation intention in old neighborhood regeneration.

Residents' participation is crucial for sustainable old neighborhood regeneration. Residents' intentions to participate in the regeneration are low in China, resulting in unsustainable neighborhood development problems. Therefore, it is essential to investigate the drivers of residents' participation. Residents' behavioral mechanisms are deeply embedded in their social networks, especially in acquaintance social networks typical of old neighborhoods in China. By constructing a mediated moderation model based on the Theory of Planned Behavior (TPB) and danwei system and taking the old neighborhood regeneration in Xi'an as a case study, this paper investigates the paths and mechanisms of the social network embeddedness, TPB, and danwei system on residents' participation intention. The results show that social network embeddedness can improve residents' intention to participate in regeneration through both direct and indirect pathways, and its indirect effect is much larger than the direct effect. Attitude, subjective norm, and perceived behavioral control significantly and positively mediated the contribution of social network embeddedness on participation intention. However, the specific mediating effect of attitude is significantly smaller than the other two. The danwei system has a significant moderating effect in the first stage of the relationship between social network embeddedness and participation intention. These imply that the extrinsic social factor of social network embeddedness is internalized as a driving force for convergence and motivation of residents' participation intentions mainly through the normative pressure and exchange of experiences between acquaintances and that the danwei system reinforces this extrinsic-intrinsic facilitation process through the danwei's "physical presence." These findings provide revelatory countermeasures for exploring the factors that motivate residents to participate actively in neighborhood regeneration and encourage their involvement at the intervention level.

Unilateral naevoid telangiectasia: A retrospective study of 11 paediatric cases.

Background Unilateral naevoid telangiectasia (UNT) is a rare disease with only sporadic cases reported. The pathogenesis remains elusive and especially in paediatric patients, effective and safe treatment is still uncertain. Objectives The purpose of this study was to summarise the clinical characteristics of UNT, explore the possible pathogenesis and evaluate the efficacy and safety of pulsed dye laser (PDL) therapy. Materials and Methods The epidemiological data, clinical manifestations, laboratory tests and pathological features of paediatric patients with UNT were retrospectively reviewed. PDL treatment was done on some of the patients. Clinical documents and patient images before and after treatment were assessed to evaluate efficacy and adverse events. Results Most of the cases (9/11) presented with unilateral lesions. The laboratory results of all the 11 cases were normal. Histological examination in six cases revealed multiple, dilated veins in the reticular dermis. Vascular endothelial growth factor (VEGF) staining was positive, whereas oestrogen receptor staining was negative. Nine cases were treated with PDL which was shown to be effective and safe. Conclusion UNT has typical clinical manifestations. The pathogenesis of this disease could be linked to VEGF; however, more research and confirmation are needed. PDL is an effective and safe treatment for UNT.

Size matters: Altering antigen specific immune tolerance by tuning size of particles.

Precisely co-delivering antigens and immunosuppressants via nano/microcarriers to antigen-presenting cells (APCs) to induce antigen-specific immune tolerance represents a highly promising strategy for treating or preventing autoimmune diseases. The physicochemical properties of nano/microcarriers play a pivotal role in regulating immune function, with particle size and surface charge emerging as crucial parameters. In particular, very few studies have investigated micron-scale carriers of antigens. Herein, various nanoparticles and microparticles (NPs/MPs) with diverse particle sizes (ranging from 200 nm to 5 µm) and surface charges were prepared. Antigen peptides (MOG35-55) and immunosuppressants were encapsulated in these particles to induce antigen-specific immune tolerance. Two emulsifiers, PVA and PEMA, were employed to confer different surface charges to the NPs/MPs. The in vitro and in vivo studies demonstrated that NP/MP-PEMA could induce immune tolerance earlier than NP/MP-PVA and that NP/MP-PVA could induce immune tolerance more slowly and sustainably, indicating that highly negatively charged particles can induce immune tolerance more rapidly. Among the different sizes and charged particles tested, 200-nm-NP-PVA and 3-µm-MP-PEMA induced the greatest immune tolerance. In addition, the combination of NPs with MPs can further improve the induction of immune tolerance. In particular, combining 200 nm-NP-PVA with 3 µm-MP-PEMA or combining 500 nm-NP-PEMA with 3 µm-MP-PVA had optimal therapeutic efficacy. This study offers a new perspective for treating diseases by combining NPs with MPs and applying different emulsifiers to prepare NPs and MPs.

Efficacy and safety of autologous platelet-rich plasma in anal fistula: a systematic review and meta-analysis.

INTRODUCTION: This study aimed to determine the efficacy and safety of autologous PRP in anal fistula. METHODS: The search was done in electronic databases such as; PubMed, Scopus, Google Scholar, Embase, and Cochrane Library. The outcomes investigated in this study were the rate of improvement, the rate of recurrence, and the rate of fecal incontinence. RESULTS: Cure, incontinence, and recurrence rates were 68% (95% CI, .60-.76), 27% (95% CI, .12-.46), and 18% (95% CI, .12-.26), respectively. The pooled improvement ratio in patients treated with PRP compared to control group was 1.35 times, which was statistically significant (pooled OR=1.35, 95% CI, 1.14-1.60, P<001). The pooled recurrence ratio in patients treated with PRP compared to control group was 1.17, which was not statistically significant (pooled OR=1.17, 95% CI, 0.44-3.11). DISCUSSION: Platelet-rich plasma is an effective method of healing people with anal fistula.

Decline in carbon emission intensity of global agriculture has stagnated recently.

Using global data for around 180 countries and territories and 170 food/feed types primarily derived from FAOSTAT, we have systematically analyzed the changes in greenhouse gas (GHG) emission intensity (GHGi) (kg CO2eq per kg protein production) over the past six decades. We found that, with large spatial heterogeneity, emission intensity decreased by nearly two-thirds from 1961 to 2019, predominantly in the earlier years due to agronomic improvement in productivity. However, in the most recent decade, emission intensity has become stagnant, and in a few countries even showed an increase, due to the rapid increase in livestock production and land use changes. The trade of final produced protein between countries has potentially reduced the global GHGi, especially for countries that are net importers with high GHGi, such as many in Africa and South Asia. Overall, a continuous decline of emission intensity in the future relies on countries with higher emission intensity to increase agricultural productivity and minimize land use changes. Countries with lower emission intensity should reduce livestock production and increase the free trade of agricultural products and improve the trade optimality.

Botulinum toxin type A injection combined with biofeedback in the treatment of spastic pelvic floor syndrome.

BACKGROUND: Spastic pelvic floor syndrome (SPFS) is a refractory pelvic floor disease characterized by abnormal (uncoordinated) contractions of the external anal sphincter and puborectalis muscle during defecation, resulting in rectal emptation and obstructive constipation. The clinical manifestations of SPFS are mainly characterized by difficult defecation, often accompanied by a sense of anal blockage and drooping. Manual defecation is usually needed during defecation. From physical examination, it is commonly observed that the patient's anal muscle tension is high, and it is difficult or even impossible to enter with his fingers. AIM: To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome. METHODS: Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome. All patients underwent pelvic floor surface electromyography assessment, anorectal dynamics examination, botulinum toxin type A injection 100 U intramuscular injection, and two cycles of biofeedback therapy. RESULTS: After the botulinum toxin A injection combined with two cycles of biofeedback therapy, the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery (P < 0.05). Moreover, the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery (P < 0.05). CONCLUSION: Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome. Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively. However, randomized controlled trials are needed.

Effects of Lime Powder on the Properties of Portland Cement-Sulphoaluminate Cement Composite System at Low Temperature.

In order to reduce the risk of early freezing damage to cement-based materials in winter construction, lime powder was used to improve the properties of the Portland cement-sulphoaluminate cement (PC-CSA) composite system at low temperatures. In this study, the effects of lime powder dosage on the properties of a PC-CSA blended system with two proportions (PC:CSA = 9:1 and 7:3) at -10 °C were investigated, and the mechanisms of improvement were revealed. The results showed that the compressive strength of the PC-CSA composite system was effectively improved, and the setting time was shortened by the addition of lime powder. Lime powder could effectively act as an early heating source in the PC-CSA composite system, as the maximum temperature of samples exposed to sub-zero temperatures was increased and the time before dropping to 0 °C was prolonged by the addition of lime powder. The extra CH generated by the hydration of lime powder provided an added hydration path for C4A3S¯, which accelerated the formation of AFt at each stage. Frozen water as well as the early frost damage were effectively decreased by lime powder because of the faster consumption of free water at an early stage. The modification of the hydration products also contributed to the denseness of the microstructure.

A decavalent composite mRNA vaccine against both influenza and COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 has had a persistent and significant impact on global public health for 4 years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.IMPORTANCEAmidst the ongoing and emerging respiratory viral threats, particularly the concurrent and sequential spread of SARS-CoV-2 and influenza, our research introduces FLUCOV-10. This novel mRNA-based combination vaccine, designed to counteract both influenza and COVID-19, by incorporating genes for surface glycoproteins from various influenza viruses and SARS-CoV-2 variants. This combination vaccine was highly effective in preclinical trials, generating strong immune responses and ensuring protection against both matching and heterologous strains of influenza viruses and SARS-CoV-2. FLUCOV-10 represents a significant step forward in our ability to address respiratory viral threats, showcasing potential as a singular, adaptable vaccine solution for global health challenges.

Dynamic functional network connectivity in patients with a mismatch between white matter hyperintensity and cognitive function.

Objective: White matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective. Methods: The resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system. Results: The 149 CSVD patients included 20 cases of "Type I mismatch," 51 cases of Type I match, 38 cases of "Type II mismatch," and 40 cases of "Type II match." Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between "Type I match" and "Type I mismatch"; the FT of States 1 and 4 differed significantly between "Type II match" and "Type II mismatch." Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between "Type I match" and "Type I mismatch," while the left MTA score differed between "Type II match" and "Type II mismatch." Conclusion: Different mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

Study of different pre-treatments in the comparison of the efficacy of photodynamic therapy for moderate to severe acne vulgaris.

OBJECTIVE: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment. METHODS: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week. RESULTS: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88% for Group A, 62% for Group B, and 36% for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time. CONCLUSION: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects.

Contrasting effects of NADPH oxidases on the fungal hyphae growth and immune responses in Pleurotus ostreatus.

Pleurotus ostreatus is one of the most consumed mushroom species, as it serves as a high-quality food, favors a rich secondary metabolism, and has remarkable adaptability to the environment and predators. In this study, we investigated the function of two key reactive oxygen species producing enzyme NADPH oxidase (PoNoxA and PoNoxB) in P. ostreatus hyphae growth, metabolite production, signaling pathway activation, and immune responses to different stresses. Characterization of the Nox mutants showed that PoNoxB played an important role in the hyphal formation of the multicellular structure, while PoNoxA regulated apical dominance. The ability of P. ostreatus to tolerate a series of abiotic stress conditions (e.g., osmotic, oxidative, membrane, and cell-wall stresses) and mechanical damage repair was enhanced with PoNoxA over-expression. PoNoxB had a greater responsibility in regulating the polysaccharide composition of the cell wall and methyl jasmonate and gibberellin GA1 biosynthesis, and improved mushroom resistance against Tyrophagus putrescentiae. Moreover, mutants were involved in the jasmonate and GA signaling pathway, and toxic protein defense metabolite production. Our findings shed light on how the oyster mushroom senses stress signals and responds to adverse environments by the complex regulators of Noxs.

Case Report: Scalp pityriasis versicolor may be a neglected problem.

Pityriasis versicolor, a common skin fungal infection, is typically observed on trunk and limb skin. Here, we highlight an unusual presentation: scalp involvement, often overlooked due to its asymptomatic, mildly scaly patches. We report four pediatric cases, emphasizing the potential underestimation of this scalp variant. This case series underscores the importance of considering this diagnosis in patients with unexplained scalp hypopigmentation, especially in males with short hair who may readily notice these subtle changes. The report contributes to the understanding of this variant's clinical presentation and emphasizes the need for awareness among clinicians to ensure accurate diagnosis and appropriate management.

A novel multi-feature fusion attention neural network for the recognition of epileptic EEG signals.

Epilepsy is a common chronic brain disorder. Detecting epilepsy by observing electroencephalography (EEG) is the main method neurologists use, but this method is time-consuming. EEG signals are non-stationary, nonlinear, and often highly noisy, so it remains challenging to recognize epileptic EEG signals more accurately and automatically. This paper proposes a novel classification system of epileptic EEG signals for single-channel EEG based on the attention network that integrates time-frequency and nonlinear dynamic features. The proposed system has three novel modules. The first module constructs the Hilbert spectrum (HS) with high time-frequency resolution into a two-channel parallel convolutional network. The time-frequency features are fully extracted by complementing the high-dimensional features of the two branches. The second module constructs a grayscale recurrence plot (GRP) that contains more nonlinear dynamic features than traditional RP, fed into the residual-connected convolution module for effective learning of nonlinear dynamic features. The third module is the feature fusion module based on a self-attention mechanism to assign optimal weights to different types of features and further enhance the information extraction capability of the system. Therefore, the system is named HG-SANet. The results of several classification tasks on the Bonn EEG database and the Bern-Barcelona EEG database show that the HG-SANet can effectively capture the contribution degree of the extracted features from different domains, significantly enhance the expression ability of the model, and improve the accuracy of the recognition of epileptic EEG signals. The HG-SANet can improve the diagnosis and treatment efficiency of epilepsy and has broad application prospects in the fields of brain disease diagnosis.

Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated, EGFR-mutated, advanced non-small cell lung cancer: data from a randomized phase III trial (AENEAS).

BACKGROUND: The initial randomized, double-blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. METHODS: Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological-BICR). The primary endpoint for this subgroup analysis was CNS progression-free survival (PFS). RESULTS: Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological-BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17-0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11-0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. CONCLUSIONS: These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03849768.

Knowledge mapping of exosomes in prostate cancer from 2003 to 2022: a bibliometric analysis.

BACKGROUND: Prostate cancer (PCa) is highly prevalent among males worldwide. The investigation of exosomes in PCa has emerged as a dynamic and important research area. To visually depict the prominent research areas and evolutionary patterns of exosomes in PCa, we performed a comprehensive analysis via bibliometric methods. METHODS: Studies were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewers, and the R package "bibliometrix" were employed to analyze the relationships and collaborations among countries/regions, organizations, authors, journals, references, and keywords. RESULTS: Over the past 20 years (2003-2022), 995 literatures on exosomes in PCa have been collected. The findings indicate a consistent upward trend in annual publications with the United States being the leading contributor. Cancers is widely recognized as the most prominent journal in this area. In total, 5936 authors have contributed to these publications, with Alicia Llorente being the most prolific. The primary keywords associated with research hotspots include "liquid biopsy", "identification", "growth", "microRNAs", and "tumor-derived exosomes". CONCLUSION: Our analysis reveals that investigating the intrinsic mechanisms of exosomes in PCa pathogenesis and exploring the potential of exosomes as biomarkers of PCa constitute the principal focal points in this domain of research.

Germline-specific RNA helicase DDX4 forms cytoplasmic granules in cancer cells and promotes tumor growth.

Cancer cells undergo major epigenetic alterations and transcriptomic changes, including ectopic expression of tissue- and cell-type-specific genes. Here, we show that the germline-specific RNA helicase DDX4 forms germ-granule-like cytoplasmic ribonucleoprotein granules in various human tumors, but not in cultured cancer cells. These cancerous DDX4 complexes contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptomic changes and affects the alternative splicing landscape of a number of genes involved in cancer growth and invasiveness, leading to compromised capability of DDX4-null cancer cells to form xenograft tumors in immunocompromised mice. Importantly, the occurrence of DDX4 granules is associated with poor survival in patients with head and neck squamous cell carcinoma and higher histological grade of prostate cancer. Taken together, these results show that the germ-granule-resembling cancerous DDX4 granules control gene expression and promote malignant and invasive properties of cancer cells.

Dimethylamine Copper(I) Halide Single Crystals: Structure, Physical Properties, and Scintillation Performance.

Hybrid copper(I) halides have garnered a significant amount of attention as potential substitutes in luminescence and scintillation applications. Herein, we report the discovery and crystal growth of new zero-dimensional compounds, (C2H8N)3Cu2I5 and (C2H8N)4Cu2Br6. The bromide and iodide have a triclinic structure with space group P1̅ and an orthorhombic structure with space group Pnma, respectively. (C2H8N)3Cu2I5 exhibits cyan emission peaking at 504 nm with a photoluminescence quantum yield (PLQY) of 34.79%, while (C2H8N)4Cu2Br6 shows yellowish-green emission peaking at 537 nm with a PLQY of 38.45%. The temperature-dependent photoluminescence data of both compounds were fitted to theoretical models, revealing that nonradiative intermediate states significantly affect thermal quenching and antiquenching. Electron-phonon interactions, the origin of emission line width broadening and peak shifting, were also investigated via fittings. The scintillation properties of (C2H8N)3Cu2I5 were evaluated, and an X-ray imaging device was successfully fabricated using (C2H8N)3Cu2I5. This work demonstrates the potentiality of copper halides in lighting and X-ray imaging applications.