Single-cell sequencing of head and neck carcinoma: Transcriptional landscape and prognostic model based on malignant epithelial cell features.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.

Dynamic changes of endothelial and stromal cilia are required for the maintenance of corneal homeostasis.

Primary cilia are distributed extensively within the corneal epithelium and endothelium. However, the presence of cilia in the corneal stroma and the dynamic changes and roles of endothelial and stromal cilia in corneal homeostasis remain largely unknown. Here, we present compelling evidence for the presence of primary cilia in the corneal stroma, both in vivo and in vitro. We also demonstrate dynamic changes of both endothelial and stromal cilia during corneal development. In addition, our data show that cryoinjury triggers dramatic cilium formation in the corneal endothelium and stroma. Furthermore, depletion of cilia in mutant mice lacking intraflagellar transport protein 88 compromises the corneal endothelial capacity to establish the effective tissue barrier, leading to an upregulation of α-smooth muscle actin within the corneal stroma in response to cryoinjury. These observations underscore the essential involvement of corneal endothelial and stromal cilia in maintaining corneal homeostasis and provide an innovative strategy for the treatment of corneal injuries and diseases.

Comparing the gut microbiota of Sichuan golden monkeys across multiple captive and wild settings: roles of anthropogenic activities and host factors.

BACKGROUND: Captivity and artificial food provision are common conservation strategies for the endangered golden snub-nosed monkey (Rhinopithecus roxellana). Anthropogenic activities have been reported to impact the fitness of R. roxellana by altering their gut microbiota, a crucial indicator of animal health. Nevertheless, the degree of divergence in gut microbiota between different anthropogenically-disturbed (AD) R. roxellana and their counterparts in the wild has yet to be elucidated. Here, we conducted a comparative analysis of the gut microbiota across nine populations of R. roxellana spanning China, which included seven captive populations, one wild population, and another wild population subject to artificial food provision. RESULTS: Both captivity and food provision significantly altered the gut microbiota. AD populations exhibited common variations, such as increased Bacteroidetes and decreased Firmicutes (e.g., Ruminococcus), Actinobacteria (e.g., Parvibacter), Verrucomicrobia (e.g., Akkermansia), and Tenericutes. Additionally, a reduced Firmicutes/Bacteroidetes ratiosuggested diminished capacity for complex carbohydrate degradation in captive individuals. The results of microbial functional prediction suggested that AD populations displayed heightened microbial genes linked to vitamin and amino acid metabolism, alongside decreased genes associated antibiotics biosynthesis (e.g., penicillin, cephalosporin, macrolides, and clavulanic acid) and secondary metabolite degradation (e.g., naphthalene and atrazine). These microbial alterations implied potential disparities in the health status between AD and wild individuals. AD populations exhibited varying degrees of microbial changes compared to the wild group, implying that the extent of these variations might serve as a metric for assessing the health status of AD populations. Furthermore, utilizing the individual information of captive individuals, we identified associations between variations in the gut microbiota of R. roxellana and host age, as well as pedigree. Older individuals exhibited higher microbial diversity, while a closer genetic relatedness reflected a more similar gut microbiota. CONCLUSIONS: Our aim was to assess how anthropogenic activities and host factors influence the gut microbiota of R. roxellana. Anthropogenic activities led to consistent changes in gut microbial diversity and function, while host age and genetic relatedness contributed to interindividual variations in the gut microbiota. These findings may contribute to the establishment of health assessment standards and the optimization of breeding conditions for captive R. roxellana populations.

Small molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in estrogen receptor-positive breast cancer overcomes tamoxifen resistance.

INTRODUCTION: Estrogen receptor (ER) positive patients compromise about 70% of breast cancers. Tamoxifen, an antagonist of ERα66 (the classic ER), is the most effective and the standard first-line drug. However, its efficacy is limited by the development of acquired resistance. METHODS: A specific inhibitor of Hsp70-Bim protein-protein interaction (PPI), S1g-2, together with an inhibitor of Hsp70-Bag3 PPI, MKT-077 and an ATP-competitive inhibitor VER155008, were used as chemical tools. Cell viability assays, co-immunoprecipitation and gene knockdown were used to investigate the role of Hsp70 in tamoxifen resistance. A xenograft model was established in which tamoxifen-resistant breast cancer (MCF-7/TAM-R) cells maintained in the presence of 5 µM tamoxifen were subcutaneously inoculated. The anti-tumor efficiency of S1g-2 was measured after a daily injection of 0.8 mg/kg for 14 days. RESULTS: It was revealed that Hsp70-Bim PPI protects ERα-positive breast cancer from tamoxifen-induced apoptosis through binding and stabilizing ERα36, rather than ERα66, resulting in sustained EGFR mRNA and protein expression. Disruption of Hsp70-Bim PPI and downregulation of ERα36 expression in tumor samples are consistent with the in vitro functions of S1g-2, resulting in about a three-fold reduction in tumor volume. CONCLUSIONS: The in vivo activity and safety of S1g-2 illustrated that it is a potential strategy for Hsp70-Bim disruption to overcome tamoxifen-resistant ER-positive breast cancer.

Yeast Bxi1/Ybh3 mediates conserved mitophagy and apoptosis in yeast and mammalian cells: convergence in Bcl-2 family.

The process of degrading unwanted or damaged mitochondria by autophagy, called mitophagy, is essential for mitochondrial quality control together with mitochondrial apoptosis. In mammalian cells, pan-Bcl-2 family members including conical Bcl-2 members and non-conical ones are involved in and govern the two processes. We have illustrated recently the BH3 receptor Hsp70 interacts with Bim to mediate both apoptosis and mitophagy. However, whether similar pathways exist in lower eukaryotes where conical Bcl-2 members are absent remained unclear. Here, a specific inhibitor of the Hsp70-Bim PPI, S1g-10 and its analogs were used as chemical tools to explore the role of yeast Bxi1/Ybh3 in regulating mitophagy and apoptosis. Using Om45-GFP processing assay, we illustrated that yeast Ybh3 mediates a ubiquitin-related mitophagy pathway in both yeast and mammalian cells through association with Hsp70, which is in the same manner with Bim. Moreover, by using Bax/Bak double knockout MEF cells, Ybh3 was identified to induce apoptosis through forming oligomerization to trigger mitochondrial outer membrane permeabilization (MOMP) like Bax. We not only illustrated a conserved ubiquitin-related mitophagy pathway in yeast but also revealed the multi-function of Ybh3 which combines the function of BH3-only protein and multi-domain Bax protein as one.

Study of high-pressure thermophysical properties of orthocarbonate Sr3CO5 using deep learning molecular dynamics simulations.

The exploration of the physical attributes of the recently discovered orthocarbonate Sr3CO5 is significant for comprehending the carbon cycle and storage mechanisms within the Earth's interior. In this study, first-principles calculations are initially used to examine the structural phase transitions of Sr3CO5 polymorphs within the range of lower mantle pressures. The results suggest that Sr3CO5 with the Cmcm phase exhibits a minimal enthalpy between 8.3 and 30.3 GPa. As the pressure exceeds 30.3 GPa, the Cmcm phase undergoes a transition to the I4/mcm phase, while the experimentally observed Pnma phase remains metastable under our studied pressure. Furthermore, the structural data of SrO, SrCO3, and Sr3CO5 polymorphs are utilized to develop a deep learning potential model suitable for the Sr-C-O system, and the pressure-volume relationship and elastic constants calculated using the potential model are in line with the available results. Subsequently, the elastic properties of Cmcm and I4/mcm phases in Sr3CO5 at high temperature and pressure are calculated using the molecular dynamics method. The results indicate that the I4/mcm phase exhibits higher temperature sensitivity in terms of elastic moduli and wave velocities compared to the Cmcm phase. Finally, the thermodynamic properties of the Cmcm and I4/mcm phases are predicted in the range of 0-2000 K and 10-120 GPa, revealing that the heat capacity and bulk thermal expansion coefficient of both phases increase with temperature, with the constant volume heat capacity gradually approaching the Dulong-Petit limit as the temperature rises.

Novel superhard semiconducting structures of C8B2N2 predicted using the first-principles approach.

Using first-principles calculations, we predicted three novel superhard semiconducting structures of C8B2N2 with a space group of P3m1. We investigated their mechanical properties and electronic structures up to 100 GPa. These three structures were successfully derived by substituting carbon (C) atoms with isoelectronic boron (B) and nitrogen (N) atoms in the P3m1 phase, which is the most stable structure of BCN and exhibits exceptional mechanical properties. Our results indicated that these structures had superior energy over previously reported t-C8B2N2, achieved by replacing C atoms in the diamond supercell with B and N atoms. To ensure their stable existence, we thoroughly examined their mechanical and dynamical stabilities, and we found that their hardness values reached 82.4, 83.1, and 82.0 GPa, which were considerably higher than that of t-C8B2N2 and even surpassing the hardness of c-BN. Calculations of the electron localization function revealed that the stronger carbon-carbon covalent bonds made them much harder than t-C8B2N2. Additionally, our further calculations of band structures revealed that these materials had indirect bandgaps of 4.164, 4.692, and 3.582 eV. These findings suggest that these materials have the potential to be used as superhard semiconductors, potentially surpassing conventional superhard materials.

Effect of Dexmedetomidine on Intraoperative Hemodynamics and Blood Loss in Patients Undergoing Spine Surgery: A Systematic Review and Meta-Analysis.

Objective Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery.Methods The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity.Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.24 - 3.58; P=0.006) and bradycardia (OR: 2.48; 95%CI: 1.57 - 3.93; P=0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95%CI: 1.06 - 3.79; P=0.03) and bradycardia (OR: 2.28; 95%CI: 1.42 - 3.66; P=0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95%CI: 1.24 - 6.82; P=0.01) and bradycardia (OR: 2.66; 95%CI: 1.53 - 4.61; P=0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95%CI: 1.41 - 17.37; P=0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95%CI: 1.05 - 6.32; P=0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95%CI: 1.06 - 6.15; P=0.04) and severe (OR: 2.45; 95%CI: 1.43 - 4.20; P=0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: -82.97; 95%CI: -109.04 - -56.90; P<0.001).Conclusions Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.

Hydrated [3+2] Cyclotelomerization of Butafulvenes to Create Multiple Contiguous Fully Substituted Carbon Centers.

The construction of multiple continuous fully substituted carbon centers, which serve as unique structural motif in natural products, is a challenging topic in organic synthesis. Herein, we report a hydrated [3+2] cyclotelomerization of butafulvenes to create contiguous fully substituted carbon backbone. In the presence of scandium triflate, all-carbon skeleton with spiro fused tricyclic ring can be constructed in high diastereoselectivity by utilizing butafulvene as the synthon. Mechanistic studies suggest that this atom-economic reaction probably proceeds through a synergistic process containing butafulvenes dimerization and nucleophilic attack by water. In addition, the tricyclic product can undergo a series of synthetic derivatizations, which highlights the potential applications of this strategy. The recyclability of Sc(OTf)3 has also been demonstrated to show its robust performance in this hydrated cyclotelomerization.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Efficacy of an mHealth App to Support Patients' Self-Management of Hypertension: Randomized Controlled Trial.

BACKGROUND: Hypertension is a significant global disease burden. Mobile health (mHealth) offers a promising means to provide patients with hypertension with easy access to health care services. Yet, its efficacy needs to be validated, especially in lower-income areas with a high-salt diet. OBJECTIVE: This study aims to assess the efficacy of an mHealth app-based intervention in supporting patients' self-management of hypertension. METHODS: A 2-arm randomized controlled trial was conducted among 297 patients with hypertension at the General Hospital of Ningxia Medical University, Ningxia Hui Autonomous Region, China. Participants selected via convenience sampling were randomly allocated into intervention and control groups. Intervention group participants were trained and asked to use an mHealth app named Blood Pressure Assistant for 6 months. They could use the app to record and upload vital signs, access educational materials, and receive self-management reminders and feedback from health care providers based on the analysis of the uploaded data. Control group participants received usual care. Blood pressure (BP) and 2 questionnaire surveys about hypertension knowledge and lifestyle behavior were used to assess all participants at baseline and 6 months. Data analysis was performed with SPSS software using 2-tailed t tests and a chi-square test. RESULTS: There were no significant differences in baseline characteristics and medication use between the 2 groups (all P>.05). After 6 months, although both groups show a significant pre-post improvement (P<.001 each), the BP control rate (ie, the proportion of patients with a systolic BP of <140 mm Hg and diastolic BP of <90 mm Hg) in the intervention group was better than that in the control group (100/111, 90.1% vs 75/115, 65.2%; P<.001). The mean systolic and diastolic BP were significantly reduced by 25.83 (SD 8.99) and 14.28 (SD 3.74) mm Hg in the intervention group (P<.001) and by 21.83 (SD 6.86) and 8.87 (SD 4.22) mm Hg in the control group (P<.001), respectively. The differences in systolic and diastolic BP between the 2 groups were significant (P<.001 and P=.01, respectively). Hypertension knowledge significantly improved only in the intervention group in both pre-post and intergroup comparisons (both P<.001). However, only intragroup improvement was observed for lifestyle behaviors in the intervention group (P<.001), including medication adherence (P<.001), healthy diet (P=.02), low salt intake (P<.001), and physical exercises (P=.02), and no significant difference was observed in the control group or on intergroup comparisons. CONCLUSIONS: This research shows that the mHealth app-based intervention has the potential to improve patient health knowledge and support self-management among them toward a healthier lifestyle, including medication adherence, low-salt diets, and physical exercises, thereby achieving optimal BP control. Further research is still needed to verify the specific effects of these interventions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026437; https://www.chictr.org.cn/showproj.html?proj=38801.

Region fine-grained attention network for accurate bone age assessment.

Bone age assessment plays a vital role in monitoring the growth and development of adolescents. However, it is still challenging to obtain precise bone age from hand radiography due to these problems: 1) Hand bone varies greatly and is always masked by the background; 2) the hand bone radiographs with successive ages offer high similarity. To solve such issues, a region fine-grained attention network (RFGA-Net) was proposed for bone age assessment, where the region aware attention (RAA) module was developed to distinguish the skeletal regions from the background by modeling global spatial dependency; then the fine-grained feature attention (FFA) module was devised to identify similar bone radiographs by recognizing critical fine-grained feature regions. The experimental results demonstrate that the proposed RFGA-Net shows the best performance on the Radiological Society of North America (RSNA) pediatric bone dataset, achieving the mean absolute error (MAE) of 3.34 and the root mean square error (RMSE) of 4.02, respectively.

A Five-Step Workflow to Manually Annotate Unstructured Data into Training Dataset for Natural Language Processing.

Natural Language Processing (NLP) is a powerful technique for extracting valuable information from unstructured electronic health records (EHRs). However, a prerequisite for NLP is the availability of high-quality annotated datasets. To date, there is a lack of effective methods to guide the research effort of manually annotating unstructured datasets, which can hinder NLP performance. Therefore, this study develops a five-step workflow for manually annotating unstructured datasets, including (1) annotator training and familiarising with the text corpus, (2) vocabulary identification, (3) annotation schema development, (4) annotation execution, and (5) result validation. This framework was then applied to annotate agitation symptoms from the unstructured EHRs of 40 Australian residential aged care facilities. The annotated corpus achieved an accuracy rate of 96%. This suggests that our proposed annotation workflow can be used in manual data processing to develop annotated training corpus for developing NLP algorithms.

Distinct signatures of gut microbiota and metabolites in primary biliary cholangitis with poor biochemical response after ursodeoxycholic acid treatment.

BACKGROUND: About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response. METHODS: This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal. RESULTS: PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy. CONCLUSION: PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.

1,25-D3 ameliorates ischemic brain injury by alleviating endoplasmic reticulum stress and ferroptosis: Involvement of vitamin D receptor and p53 signaling.

Endoplasmic reticulum stress (ERS) and ferroptosis are linked to cerebral ischemia reperfusion injury (CIRI). The neuroprotective properties of 1α, 25-dihydroxyvitamin D3 (VitD3 or 1,25-D3) have been well established; however, the mechanism by which VitD3 treats CIRI through ERS and ferroptosis has not been examined. Hence, we developed middle cerebral artery occlusion/reperfusion (MCAO/R) model in SD rats to ascertain if VitD3 preconditioning mediates ERS and ferroptosis involving of p53 signaling. In this study, we observed that VitD3 can reduce infarction volume and cerebral edema, which leads to the improvement of nerve function. HE, Nissl and Tunel staining showed that VitD3 treatment significantly improved the morphology of neuronal cells and reduced their death. The expression and activation of Vitamin D receptor (VDR), PKR-like ER kinase (PERK), C/EBP-homologous protein (CHOP), p53, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and reactive oxygen species (ROS) in the ischemic penumbral area were detected by real-time qPCR, Western-blotting and Elisa. The results showed that after VitD3 treatment, VDR increased, ERS-related indices (PERK, CHOP) significantly decreased and ferroptosis-related indices (Nrf2, GPX4) increased. As a VDRs antagonist, pyridoxal-5-phosphate (P5P) can partially block the neuroprotective effects of VitD3. Therefore, CIRI can induce ERS and ferroptosis in the ischemic penumbra area and VitD3 may ameliorate nerve damage in CIRI rats by up-regulating VDR, alleviating p53-associated ERS and ferroptosis.

Automatic IMRT treatment planning through fluence prediction and plan fine-tuning for nasopharyngeal carcinoma.

BACKGROUND: At present, the implementation of intensity-modulated radiation therapy (IMRT) treatment planning for geometrically complex nasopharyngeal carcinoma (NPC) through manual trial-and-error fashion presents challenges to the improvement of planning efficiency and the obtaining of high-consistency plan quality. This paper aims to propose an automatic IMRT plan generation method through fluence prediction and further plan fine-tuning for patients with NPC and evaluates the planning efficiency and plan quality. METHODS: A total of 38 patients with NPC treated with nine-beam IMRT were enrolled in this study and automatically re-planned with the proposed method. A trained deep learning model was employed to generate static field fluence maps for each patient with 3D computed tomography images and structure contours as input. Automatic IMRT treatment planning was achieved by using its generated dose with slight tightening for further plan fine-tuning. Lastly, the plan quality was compared between automatic plans and clinical plans. RESULTS: The average time for automatic plan generation was less than 4 min, including fluence maps prediction with a python script and automated plan tuning with a C# script. Compared with clinical plans, automatic plans showed better conformity and homogeneity for planning target volumes (PTVs) except for the conformity of PTV-1. Meanwhile, the dosimetric metrics for most organs at risk (OARs) were ameliorated in the automatic plan, especially Dmax of the brainstem and spinal cord, and Dmean of the left and right parotid glands significantly decreased (P < 0.05). CONCLUSION: We have successfully implemented an automatic IMRT plan generation method for patients with NPC. This method shows high planning efficiency and comparable or superior plan quality than clinical plans. The qualitative results before and after the plan fine-tuning indicates that further optimization using dose objectives generated by predicted fluence maps is crucial to obtain high-quality automatic plans.

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis.

PURPOSE: Keratoconus (KC) is a multifactorial disorder. This study aimed to conduct a systematic meta-analysis to exclusively explore the candidate proteins associated with KC pathogenesis. METHODS: Relevant literature published in the last ten years in Pubmed, Web of Science, Cochrane, and Embase databases were searched. Protein expression data were presented as the standard mean difference (SMD) and 95% confidence intervals (CI). The meta-analysis is registered on PROSPERO, registration number CRD42022332442 and was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA). GO and KEGG enrichment analysis were performed, as well as the miRNAs and chemicals targeting the candidate proteins were predicted. PPI was analyzed to screen the hub proteins, and their expression was verified by RT-qPCR. RESULTS: A total of 21 studies were included in the meta-analysis, involving 346 normal eyes and 493 KC eyes. 18 deregulated proteins with significant SMD values were subjected to further analysis. In which, 7 proteins were up-regulated in KC compared with normal controls, including IL6 (SMD 1.54, 95%CI [0.85, 2.24]), IL1B (SMD 2.07, 95%CI [0.98, 3.16]), TNF (SMD 2.1, 95%CI [0.24, 3.96]), and MMP9 (SMD 1.96, 95%CI [0.68, 3.24]). While 11 proteins were down-regulated in KC including LOX (SMD 2.54, 95%CI [-4.51, -0.57]). GO and KEGG analysis showed that the deregulated proteins were involved in inflammation, extracellular matrix (ECM) remodeling, and apoptosis. MMP9, IL6, LOX, TNF, and IL1B were regarded as hub proteins according to the PPI analysis, and their transcription changes in stromal fibroblasts of KC were consistent with the results of the meta-analysis. Moreover, 10 miRNAs and two natural polyphenols interacting with hub proteins were identified. CONCLUSION: This study obtained 18 candidate proteins and demonstrated altered cytokine profiles, ECM remodeling, and apoptosis in KC patients through meta-analysis and bioinformatic analysis. It will provide biomarkers for further understanding of KC pathogenesis, and potential therapeutic targets for the drug treatment of KC.

Effects of different extraction methods on the structural and biological properties of Hericium coralloides polysaccharides.

In current study, polysaccharides from Hericium coralloides were extracted by heat reflux, acid-assisted, alkali-assisted, enzyme-assisted, ultrasonic-assisted, cold water, pressurized hot water, hydrogen peroxide/ascorbic acid system and acid-chlorite delignification methods, which were named as HRE-P, ACE-P, AAE-P, EAE-P, UAE-P, CWE-P, PHE-P, HAE-P, and ACD-P, respectively. Their physicochemical properties, structural characteristics, and antioxidant activities were investigated and compared. Experimental outcomes indicated notable variations in the extraction yields, chemical compositions, monosaccharide constituents and molecular weights of the obtained nine polysaccharides. HRE-P demonstrated the highest activity against ABTS and OH radicals, CWE-P against ABTS, DPPH, and superoxide radicals, and UAE-P against DPPH radicals. In addition, UAE-P, CWE-P, and HAE-P exhibited better protective effects on L929 cells, when compared to the other obtained polysaccharides. Additionally, correlation analysis indicated that monosaccharide composition and total polyphenol content were two prominent variables influencing the bioactivity of H. coralloides polysaccharides.

Cyanobacterial blooms in Lake Taihu: Temporal trends and potential drivers.

Lake Taihu, an inland lake, frequently experiences Cyanobacterial blooms that have historically posed severe threats to its aquatic ecosystem. Combining field observations and satellite remote-sensed data, factors that influence algal bloom intensity in Lake Taihu over an eight-year period, from 2016 to 2023, are examined, and changes in phytoplankton community composition, climate, water quality, economic activities, and food web dynamics are reported. Sentinel-2 MSI data analysis reveals a dramatic decrease in Cyanobacterial blooms in 2023, with a reduction in the annual maximum bloom area of 76.90 % from 2016 values. From 2016 to 2022, the ratio of Cyanobacteria to other phytoplankton ranged 82.09 %-98.29 %, but in 2023, this dropped to 60.98 %. Concurrently, Cyanobacteria density dropped to an historic low of 2.29 × 107 cells/L (16.4 % of 2021 peak values). Redundancy and random forest analyses indicated that nitrogen has a greater influence on phytoplankton than phosphorus, with temperature and permanganate index being the important parameters to affect phytoplankton community structure. We attribute the decrease in Cyanobacterial blooms in Lake Taihu in 2023 to be largely caused by shifts in phytoplankton community structure, particularly the sharp decline in Microcystis sp. density, a genus often linked to bloom formation. Meteorological conditions such as reduced rainfall and wind speed during the winter and spring of 2023 also contributed to diminishing Cyanobacterial blooms. Ongoing improvements in water quality, reduced economic activities because of pandemic restrictions, and implementation of a fishing ban since 2020 have likely further contributed to reductions in bloom frequency. These results improve our understanding of the processes that affect algal blooms in Lake Taihu, and potentially other eutrophic inland lakes.

A theoretical investigation on the structural stability, superconductivity, and optical and thermodynamic properties of Ir2P under pressure.

The potential applications of Ir2P are promising due to its desirable hardness, but its fundamental properties are still not fully understood. In this study, we present a systematic investigation of Ir2P's structural, electronic, superconducting, optical, and thermodynamic properties of Ir2P under pressure. Our calculations show that Ir2P has a Fm3̄m structure at ambient pressure, which matches well with experimental data obtained from high-pressure synchrotron X-ray diffraction. As pressure increases, a transition from the Fm3̄m to the I4/mmm phase occurs at 103.4 GPa. The electronic structure and electron-phonon coupling reveal that the Fm3̄m and I4/mmm phases of Ir2P are superconducting materials with superconducting transition temperatures of 2.51 and 0.89 K at 0 and 200 GPa, respectively. The optical properties of Ir2P indicate that it has optical conductivity in the infrared, visible, and ultraviolet regions. Additionally, we observed that the reflectivity R(ω) of Ir2P is higher than 76% in the 25-35 eV energy range at different pressures, which suggests that it could be used as a reflective coating. We also explored the finite-temperature thermodynamic properties of Ir2P, including the Debye temperature, the first and second pressure derivatives of the isothermal bulk modulus, and the thermal expansion coefficient up to 2000 K using the quasi-harmonic Debye model. Our findings offer valuable insights for engineers to design better devices.