Air Change Rate and SARS-CoV-2 Exposure in Hospitals and Residences: A Meta-Analysis.

As SARS-CoV-2 swept across the globe, increased ventilation and implementation of air cleaning were emphasized by the US CDC and WHO as important strategies to reduce the risk of inhalation exposure to the virus. To assess whether higher ventilation and air cleaning rates lead to lower exposure risk to SARS-CoV-2, 1274 manuscripts published between April 2020 and September 2022 were screened using key words "airborne SARS-CoV-2 or "SARS-CoV-2 aerosol". Ninety-three studies involved air sampling at locations with known sources (hospitals and residences) were selected and associated data were compiled. Two metrics were used to assess exposure risk: SARS-CoV-2 concentration and SARS-CoV-2 detection rate in air samples. Locations were categorized by type (hospital or residence) and proximity to the sampling location housing the isolated/quarantined patient (primary or secondary). The results showed that hospital wards had lower airborne virus concentrations than residential isolation rooms. A negative correlation was found between airborne virus concentrations in primary-occupancy areas and air changes per hour (ACH). In hospital settings, sample positivity rates were significantly reduced in secondary-occupancy areas compared to primary-occupancy areas, but they were similar across sampling locations in residential settings. ACH and sample positivity rates were negatively correlated, though the effect was diminished when ACH values exceeded 8. While limitations associated with diverse sampling protocols exist, data considered by this meta-analysis support the notion that higher ACH may reduce exposure risks to the virus in ambient air.

Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated. METHODS: We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (three each from CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. RESULTS: Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. CONCLUSIONS: Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Application of a feedforward control-based intervention for preventing hypothermia in trauma patients in a pre-hospital emergency setting.

OBJECTIVE: To investigate the efficacy of a feedforward control-based intervention strategy for preventing hypothermia among trauma patients during pre-hospital emergency care. METHODS: We conducted a retrospective analysis comparing trauma patients treated before and after implementing the intervention, with 40 cases in each group. All patients received emergency care from the Fuzhou Emergency Center on the scene. Multivariate analysis was used to explore the risk factors for hypothermia. The effective rate, incidence of adverse reactions, quality of body temperature management, medical staff's knowledge, attitudes, and behaviors regarding mild hypothermia prevention, coagulation function, treatment time at various stages, prognosis score, and treatment situation were compared between the two groups. RESULTS: The adverse reactions, intervention methods, and degree of cognitive improvement were influencing factors for hypothermia. The effective rate (92.50%) in the feedforward control group was higher than that in the non-feedforward control group (65.00%), with a lower incidence of adverse reactions (2.50%). The temperature management quality score of the feedforward control group (6.23±0.62) was higher. The feedforward control group achieved a higher quality score for temperature management (6.23±0.62) and exhibited a greater understanding of hypothermia prevention among trauma patients (P<0.05). Compared to the non-feedforward control group, the feedforward control group showed improved coagulation function, better performance in treatment time at each node, and higher prognosis scores. CONCLUSION: The intervention model based on feedforward control can effectively improve the standard of pre-hospital emergency care and prevent the incidence of hypothermia in trauma patients.

The BioCascade Impactor: A novel device for direct collection of size-fractionated bioaerosols into liquid medium.

The ability to collect size-fractionated airborne particles that contain viable bacteria and fungi directly into liquid medium while also maintaining their viability is critical for assessing exposure risks. In this study, we present the BioCascade impactor, a novel device designed to collect airborne particles into liquid based on their aerodynamic diameter in three sequential stages (>9.74 µm, 3.94-9.74 µm, and 1.38-3.94 µm when operated at 8.5 L/min). Aerosol samples containing microorganisms - either Saccharomyces kudriavzevii or Micrococcus luteus, were used to evaluate the performance of the BioCascade (BC) paired with either the VIable Virus Aerosol Sampler (VIVAS) or a gelatin filter (GF) as stage 4 to collect particles <1.38 µm. Stages 2 and 3 collected the largest fractions of viable S. kudriavzevii when paired with VIVAS (0.468) and GF (0.519), respectively. Stage 3 collected the largest fraction of viable M. luteus particles in both BC+VIVAS (0.791) and BC+GF (0.950) configurations. The distribution function of viable microorganisms was consistent with the size distributions measured by the Aerodynamic Particle Sizer. Testing with both bioaerosol species confirmed no internal loss and no re-aerosolization occurred within the BC. Irrespective of the bioaerosol tested, stages 1, 3 and 4 maintained ≥80% of viability, while stage 2 maintained only 37% and 73% of viable S. kudriavzevii and M. luteus, respectively. The low viability that occurred in stage 2 warrants further investigation. Our work shows that the BC can efficiently size-classify and collect bioaerosols without re-aerosolization and effectively maintain the viability of collected microorganisms.

Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy.

Although the use of Doxorubicin (Dox) is extensive in the treatment of malignant tumor, the toxic effects of Dox on the heart can cause myocardial injury. Therefore, it is necessary to find an alternative drug to alleviate the Dox-induced cardiotoxicity. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which is an active ingredient of Artemisia annua. The study investigates the effects of DHA on doxorubicin-induced cardiotoxicity and ferroptosis, which are related to the activation of Nrf2 and the regulation of autophagy. Different concentrations of DHA were administered by gavage for 4 weeks in mice. H9c2 cells were pretreated with different concentrations of DHA for 24 h in vitro. The mechanism of DHA treatment was explored through echocardiography, biochemical analysis, real-time quantitative PCR, western blotting analysis, ROS/DHE staining, immunohistochemistry, and immunofluorescence. In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes. In vitro, DHA attenuated oxidative stress and cardiomyocyte ferroptosis, activated Nrf2, promoted clearance of autophagosomes, and reduced lysosomal destruction. The changes of ferroptosis and Nrf2 depend on selective degradation of keap1 and recovery of lysosome. We found for the first time that DHA could protect the heart from the toxic effects of Dox-induced cardiotoxicity. In addition, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.

The BioCascade-VIVAS system for collection and delivery of virus-laden size-fractionated airborne particles.

The size of virus-laden particles determines whether aerosol or droplet transmission is dominant in the airborne transmission of pathogens. Determining dominant transmission pathways is critical to implementing effective exposure risk mitigation strategies. The aerobiology discipline greatly needs an air sampling system that can collect virus-laden airborne particles, separate them by particle diameter, and deliver them directly onto host cells without inactivating virus or killing cells. We report the use of a testing system that combines a BioAerosol Nebulizing Generator (BANG) to aerosolize Human coronavirus (HCoV)-OC43 (OC43) and an integrated air sampling system comprised of a BioCascade impactor (BC) and Viable Virus Aerosol Sampler (VIVAS), together referred to as BC-VIVAS, to deliver the aerosolized virus directly onto Vero E6 cells. Particles were collected into four stages according to their aerodynamic diameter (Stage 1: >9.43 µm, Stage 2: 3.81-9.43 µm, Stage 3: 1.41-3.81 µm and Stage 4: <1.41 µm). OC43 was detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) analyses of samples from all BC-VIVAS stages. The calculated OC43 genome equivalent counts per cm3 of air ranged from 0.34±0.09 to 70.28±12.56, with the highest concentrations in stage 3 (1.41-3.81 µm) and stage 4 (<1.41 µm). Virus-induced cytopathic effects appeared only in cells exposed to particles collected in stages 3 and 4, demonstrating the presence of viable OC43 in particles <3.81 µm. This study demonstrates the dual utility of the BC-VIVAS as particle size-fractionating air sampler and a direct exposure system for aerosolized viruses. Such utility may help minimize conventional post-collection sample processing time required to assess the viability of airborne viruses and increase the understanding about transmission pathways for airborne pathogens.

Stigma and Stigma Resilience: Role of the Undergraduate and the Campus Environment.

RATIONALE: Stigma permeates disability experiences and compounds disability-related challenges. OBJECTIVE: Identify individual and environmental factors of stigmatizing experiences of college students with learning disabilities (LDs) and attention-deficit/hyperactivity disorder (ADHD). METHODOLOGY: A qualitative descriptive design was used with a thematic analysis of 30 transcripts from group discussions among four cohorts of undergraduates with LD/ADHD (N = 52). The Person-Environment-Occupation-Performance Model was used in interpreting the stigmatizing experiences. FINDINGS: The themes Perceived Misconceptions and Stigmatizing Actions describe key social-environmental factors. The theme Overcoming Stigmatizing Experiences elucidates key skills and processes for developing stigma resilience. These skills and processes were anchored in self-awareness and personally contextualized understanding of disability-related challenges and strengths, which were fostered during positive interactions with supportive others, such as instructors and mentors. IMPLICATIONS: Findings illustrate the biopsychosocial nature of stigma and highlight the role of individual and social-environmental factors in building stigma resilience among young adults with LD/ADHD.

Understanding Stigma and Resilience Among College Students with Learning Disabilities and ADHDWe studied how college students with learning disabilities (LDs) and attention-deficit/hyperactivity disorder (ADHD) experience stigma, which means feeling judged or treated unfairly because of their disabilities. We talked to 52 undergraduates in four groups to understand their experiences and found three main things related to stigma. First, students feel like others have wrong ideas about them and their disabilities. Second, they experience actions from others that make them feel stigmatized. Third, they develop ways to overcome these experiences. Students became more resilient to stigma when they understood themselves better and had support from others like teachers and mentors. Stigma is not just a personal thing for students with LD/ADHD; but it is also influenced by the people around them and how they see themselves.

Real-time monitoring of abnormal mitochondrial viscosity in glioblastoma with a novel mitochondria-targeting fluorescent probe.

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

A long non-coding RNA functions as a competitive endogenous RNA to modulate TaNAC018 by acting as a decoy for tae-miR6206.

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.

Molecular and Family Analyses of a Novel RHD1058G>C Allele in a Chinese RhD Population.

BACKGROUND: Rh(D) phenotype in a sample from a 19-year-old female patient showed weak positivity (1+). A follow-up sample was requested to further define the Rh(D) phenotype, her Rh(D) phenotype was tested by using another reagent, Rh(D) phenotype still showed weak reactivity (1+), RhCcEe phenotype was Ccee. METHODS: Seven samples from the family members of the proposita were received. The RhDCcEe phenotypes were typed by the microcolumn gel card and the unexpected antibodies were assayed by indirect anti-human globulin test (IAT). Genomic DNA was extracted from the blood sample and the novel RHD1058G>C allele was detected through an established sequence-specific primer PCR (PCR-SSP), RHD exons 1 - 10 were sequenced afterward by exon-specific amplification. The distribution of RHD1058G>C allele and RHD weak positive phenotype were investigated in the pedigrees. RESULTS: The unexpected antibodies all were negative in the family members. The novel RHD1058G>C allele was found in the proposita, her father, and grandfather. Five family members were detected serologically with the common Rh(D)-positive phenotypes either as homozygote of RHD/RHD or heterozygote of RHD/RHd. Two family members were detected as weak D phenotypes in accordance with the genotyping results by PCR-SSP, and both of them have a D1058Ce haplotype and a dce haplotype. One member, her father, was tested common Rh(D)-positive with D1058Ce haplotype and a Dce haplotype. CONCLUSIONS: These data allow us to describe the characteristics of the weak D phenotype with a novel c.RHD-1058G>C allele, which may be partial D and increase the risk of RHD alloantibody. The novel RHD1058G>C allele was inherited in three generations in a family rather than spontaneous mutation in an individual.

Urgent Management of Penetrating Ocular Injury: A Case Report and Review of the Literature.

Ocular globe injury is a severe ophthalmic emergency that requires immediate attention in the emergency department. In this case report, we present a 35-year-old male who suffered a penetrating ocular injury and globe rupture caused by a nail puncture. The patient presented with severe pain and visual loss and was treated with tetanus vaccination, empirical antibiotics, and pain control, followed by an urgent orbital computed tomography (CT) scan and consultation with an ophthalmologist. The CT scan revealed a retained nail in the ocular space, and an urgent operation was performed to repair the eyeball rupture, remove the intraocular foreign body, and perform an anterior vitrectomy. The patient was discharged 6 days after the operation with a visual acuity of 20/400 and an ocular trauma score of 34. This case highlights the importance of initial emergency physician decision-making and the need for a thorough history-taking and examination when encountering penetrating ocular injuries.

Nuclear transport of phosphorylated LanCL2 promotes invadopodia formation and tumor progression of glioblastoma by activating STAT3/Cortactin signaling.

INTRODUCTION: Our previous study showed that the abscisic acid receptor lanthionine synthetase C-like 2 (LanCL2) is a significant prognostic factor for overall survival in young glioblastoma patients. However, the role of LanCL2 in glioblastoma remains unclear yet. OBJECTIVES: This study aims to investigate the role of LanCL2 in regulating in-vitro cell invasion and in-vivo tumor progression of glioblastoma and its underlying mechanism. METHODS: Tyrosine 198 or 295 residue of LanCL2 was mutated using site-directed mutagenesis to block its phosphorylation. The role of LanCL2 in glioblastoma was investigated using transwell or 3D invasion assay, matrix degradation assay and intracranial xenograft model. RESULTS: This study showed that nuclear transport of LanCL2 was enhanced by overexpression of LanCL2 or its ligand abscisic acid in glioblastoma cells. Knockdown of LanCL2 suppressed migration, invasion and invadopodia formation of glioblastoma cells, whereas overexpression of wild-type LanCL2 enhanced them. Blocking of Tyr295 residue phosphorylation of LanCL2 impeded its nuclear transport, retarded glioblastoma cell motility and invadopodia formation, and deceased the phosphorylation of Cortactin and STAT3. c-Met was identified as the upstream tyrosine kinase of Tyr295 residue of LanCL2, and inhibition of c-Met markedly suppressed the nuclear transport of LanCL2. Moreover, overexpression of wild-type LanCL2 significantly promoted orthotopic tumor growth of glioblastoma in vivo and led to poor survival of mice with median survival time of 33.5 days, whereas Tyr295 mutation rescued it with median survival time of 49 days. CONCLUSION: Our findings suggested that Tyr295 phosphorylation is crucial to the activation and nuclear transport of LanCL2, as well as invadopodia formation and tumor progression of glioblastoma, providing the evidence of a novel signaling axis c-Met/LanCL2/STAT3/Cortactin and the first observation of the importance of Tyr295 phosphorylation to LanCL2.

Therapeutic Application of Dendrobium fimbriatum Hook for Retinopathy Caused by Ultraviolet Radiation and Chemotherapy Using ARPE-19 Cells and Mouse Retina.

Retinopathy caused by ultraviolet radiation and cancer chemotherapy has increased dramatically in humans due to rapid environmental and social changes. Therefore, it is very important to develop therapeutic strategies to effectively alleviate retinopathy. In China, people often choose dendrobium to improve their eyesight. In this study, we explored how Dendrobium fimbriatum extract (DFE) protects ARPE-19 cells and mouse retinal tissue from damage of ultraviolet (UV) radiation and chemotherapy. We evaluated the antioxidant capacity of DFE using the 1,1-diphenyl-2-trinitophenylhydrazine (DPPH) assay. The protective effects of DEF from UV- and oxaliplatin (OXA)-induced damage were examined in ARPE-19 cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and immunofluorescence (IF) stains, and in mouse retinal tissue using immunohistochemistry (IHC) stains. Our results show that DFE has excellent antioxidant capacity. The ARPE-19 cell viability was decreased and the F-actin cytoskeleton structure was damaged by UV radiation and OXA chemotherapy, but both were alleviated after the DFE treatment. Furthermore, DFE treatment can alleviate OXA chemotherapy-induced reduced expressions of rhodopsin and SOD2 and increased expressions of TNF-α and caspase 3 in mouse retinal tissue. Thus, we suggest that DFE can act as suitable treatment for retinopathy through reducing oxidative stress, inflammation, and apoptosis.

Proteomics analysis of enzyme systems and pathway changes during the moromi fermentation of soy sauce mash.

BACKGROUND: During the brewing of soy sauce, the conversion of multiple substances is driven by various microorganisms and their secreted enzyme systems. Soy sauce mash is an important source of enzyme systems during moromi fermentation, but the changes of enzyme systems in soy sauce mash during moromi fermentation are poorly understood. In order to explore the predominant enzyme systems existing during moromi fermentation and to explain the characteristics of the enzyme system changes, an enzymatic activities assay and 4D-label-free proteomics analysis were conducted on soy sauce mash at different stages of fermentation. RESULTS: The activities of hydrolytic enzymes in soy sauce mash decreased continuously throughout the fermentation process, while most of the characteristic physicochemical substances in soy sauce mash supernatant had already accumulated at the early stage of fermentation. Four hydrolytic enzymes were found to be positively correlated with important physicochemical indexes by principal component analysis and Pearson correlation analysis. The proteomics analysis revealed three highly upregulated enzymes and two enzymes that were present in important metabolic pathways throughout the fermentation process. Furthermore, it was found that Aspergillus oryzae was able to accumulate various nutrients in the soy sauce mash by downregulating most of its metabolic pathways. CONCLUSION: Enzymes present with excellent properties during the moromi fermentation period could be obtained from these results. Meanwhile, the characterization of the metabolic pathways of microorganisms during the moromi fermentation period was revealed. The results provide a basis for more scientific and purposeful improvement of moromi fermentation in the future. © 2024 Society of Chemical Industry.

Production of docosahexaenoic acid by a novel isolated Aurantiochytrium sp. 6-2 using fermented defatted soybean as a nitrogen source for sustainable fish feed development.

We focused on the production of docosahexaenoic acid (DHA)-containing microbial lipids by Aurantiochytrium sp. using of defatted soybean (DS) as a nitrogen source. Defatted soybean is a plant biomass that could provide a sustainable supply at a low cost. Results showed that Aurantiochytrium sp. could not directly assimilate the DS as a nitrogen source but could grow well in a medium containing DS fermented with rice malt. When cultivated in a fermented DS (FDS) medium, Aurantiochytrium sp. showed vigorous growth with the addition of sufficient sulfate and chloride ions as inorganic nutrients without seawater salt. A novel isolated Aurantiochytrium sp. 6-2 showed 15.8 ± 3.4 g/L DHA productivity (in 54.8 ± 12.1 g/L total fatty acid production) in 1 L of the FDS medium. Therefore, DHA produced by Aurantiochytrium sp. using FDS enables a stable and sustainable DHA supply and could be an alternative source of natural DHA derived from fish oil.

Melanoma biology and treatment: a review of novel regulated cell death-based approaches.

The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The treatment of advanced melanoma, particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates of approximately 50% for patients with advanced melanoma. However, therapy resistance and inadequate treatment response continue to hinder further breakthroughs in treatments that increase survival rates. This review provides an introduction to the molecular-level pathogenesis of melanoma and offers an overview of current treatment options and their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is an orderly cell death controlled by a variety of macromolecules to maintain the stability of the internal environment. Since the uncontrolled proliferation of tumor cells requires evasion of RCD programs, inducing the RCD of melanoma cells may be a treatment strategy. This review summarizes studies on various types of nonapoptotic RCDs, such as autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and the recently discovered cuproptosis, in the context of melanoma. The relationships between these RCDs and melanoma are examined, and the interplay between these RCDs and immunotherapy or targeted therapy in patients with melanoma is discussed. Given the findings demonstrating melanoma cell death in response to different stimuli associated with these RCDs, the induction of RCD shows promise as an integral component of treatment strategies for melanoma.

PHDtools: A platform for pathogen detection and multi-dimensional genetic signatures decoding to realize pathogen genomics data analyses online.

OBJECTIVES: Facing the emerging diseases, rapid identification of the pathogen and multi-dimensional characterization of the genomic features at both isolate-level and population-level through high-throughput sequencing data can provide invaluable information to guide the development of antiviral agents and strategies. However, a user-friendly program is in urgent need for clinical laboratories without bioinformatics background to decode the complex big genomics data. METHODS: In this study, we developed an interactive online platform named PHDtools with a total of 15 functions to analyze metagenomics data to identify the potential pathogen and decode multi-dimensional genetic signatures including intra-/inter-host variations and lineage-level variations. The platform was applied to analyze the meta-genomic data of the samples collected from the 172 imported COVID-19 cases. RESULTS: According to the analytical results of mNGS, 27 patients were found to have the co-infections of SARS-CoV-2 with either influenza virus (n = 9) or human picobirnavirus (n = 19). Enough coverages of all the assembled SARS-CoV-2 genomes provided the sub-lineages of Omicron variant, and the number of mutations in the non-structural genes and M gene was increased, as well as the intra-host variations occurred in E and M gene were under positive selection (Ka/Ks > 1). These findings of increased or changed mutations in the SARS-CoV-2 genome characterized the current adaptive evolution patterns of Omicron sub-lineages, and revealed the evolution speed of these sub-lineages might increase. CONCLUSIONS: Consequently, the application of PHDtools has proved that this platform is accurate, user-friendly and convenient for clinical users who are deficient in bioinformatics, and the clinical monitor of SARS-CoV-2 genomes by PHDtools also highlighted the potential evolution features of current SARS-CoV-2 and indicated that the development of anti-SARS-CoV-2 agents and new-designed vaccines should incorporate the gene variations other than S gene.

Vertical variation of source-apportioned PM2.5 and selected volatile organic compounds near an elevated expressway in an urban area.

Fine particulate matter (PM2.5) and volatile organic compounds (VOCs) are associated with adverse health effects and show spatial variation in three dimensions. The present study attempted to evaluate source contributions of PM2.5 and toxic VOCs in a metropolitan area focusing on the associated vertical variations. A special emphasis is put on the effects of the elevated expressway on the vertical variability of contribution estimates of the identified sources. Nine source factors, i.e., soil dust, sea salt/oil combustion, secondary nitrate, industrial emission, aged VOCs/secondary aerosol, traffic-related I, solvent use/industrial process, secondary sulfate, and traffic-related II, were identified using positive matrix factorization (PMF). The main contributors to PM2.5 were secondary sulfate (19.1%) and traffic-related emissions (traffic-related I and II, 16.1%), whereas the largest contributors to VOCs were traffic-related emissions (37.6%). The influence of the elevated expressway is suggested to be particularly critical on vertical variations of traffic-related emissions, including aging and secondary formation of locally accumulated air pollutants near roads. Increasing the building porosity under the viaduct could reduce the accumulation of air pollutants caused by the shelter effect. Additionally, in-street barriers would be beneficial in reducing population exposure to traffic-related emissions by altering the airflows near roads.

Microplastics are detected in human gallstones and have the ability to form large cholesterol-microplastic heteroaggregates.

Ubiquitous pollution due to microplastics through the food chain is a major cause of various deleterious effects on the human health. The aim of this study was to determine the existence of microplastics and the internal mechanism of microplastics as accelerators of cholelithiasis. Gallstones were collected from 16 patients after cholecystectomy, and microplastics in the gallstones were detected through laser direct infrared and pyrolysis gas chromatographymass spectrometry examinations. Mice model of gallstone were constructed with or without different diameters of microplastic (0.5, 5 and 50 µm). The affinity between microplastic and cholesterol or bilirubin was tested by co-culturing and qualified using molecular dynamics simulations. Finally, altered gut microbiota among the groups were identified using 16 s rRNA sequencing. The presence of microplastics in the gallstones of all the patients were confirmed. Microplastic content was significantly higher in younger chololithiasis patients (age<50 years). Mice fed a high-cholesterol diet with microplastic drinks showed more severe chololithiasis. In terms of the mechanism, microplastics showed a higher affinity for cholesterol than for bilirubin. Significant alterations in the gut microbiota have also been identified after microplastic intake in mice. Our study revealed the presence of microplastics in human gallstones, showcasing their potential to aggravate chololithiasis by forming large cholesterol-microplastic heteroaggregates and altering the gut microbiota.