Hyper-Cross-Linked Polyindole for Selective Adsorption and Resource Utilization of Organic Pollutants in Water.

Efficient treatment and utilization of organic pollutants in water are difficult for environmental remediation. A new hyper-cross-linked polymer (PIn-HCP) with high specific surface area was constructed via polyindole (PIn) as building blocks. Rich pore structures and abundant adsorption sites in PIn-HCP were obtained by hyper-cross-linking. The specific surface area of PIn-HCP was enhanced from 14.85 to 431.89 m2/g. The adsorption capacities of PIn-HCP-2 for methylene blue (MB), methyl orange (MO), rhodamine B (RhB), and tetracycline hydrochloride (TH) are 902.0, 275.2, 16.0, and 0.0 mg/g, respectively. PIn-HCP also realized selective adsorption of MB, which can better separate MB/RhB and MB/TH. MB is adsorbed onto PIn-HCP via a synergistic mechanism including π-π stacking, electrostatic interaction, cation-π interaction, hydrogen bonding interaction, and ion exchange. The huge conjugated structure of PIn promotes PIn-HCP to selectively adsorb MB. In addition, PIn-HCP also retains the electrochemical properties of PIn. MB can improve the specific capacitance of PIn-HCP up to five times, and it has potential as a supercapacitor electrode. PIn-HCP offers a promising and practical solution for the efficient treatment and utilization of organic pollutants in water.

METTL14 promotes chondrocyte ferroptosis in osteoarthritis via m6A modification of GPX4.

BACKGROUND: Ferroptosis is caused by iron-dependent peroxidation of membrane phospholipids and chondrocyte ferroptosis contributes to osteoarthritis (OA) progression. Glutathione peroxidase 4 (GPX4) plays a master role in blocking ferroptosis. N6-methyladenosine (m6A) is an epigenetic modification among mRNA post-transcriptional modifications. This study investigated the effect of methyltransferase-like 14 (METTL14), the key component of the m6A methyltransferase, on chondrocyte ferroptosis via m6A modification. METHODS: An OA rat model was established through an intra-articular injection of monosodium iodoacetate in the right knee. OA cartilages in rat models were used for gene expression analysis. Primary mouse chondrocytes or ADTC5 cells were stimulated with IL-1ß or erastin. The m6A RNA methylation quantification kit was used to measure m6A level. The effect of METTL14 and GPX4 on ECM degradation and ferroptosis was investigated through western blotting, fluorescence immunostaining, propidium iodide staining, and commercially available kits. The mechanism of METTL14 action was explored through MeRIP-qPCR assays. RESULTS: METTL14 and m6A expression was upregulated in osteoarthritic cartilages and IL-1ß-induced chondrocytes. METTL14 depletion repressed the IL-1ß or erastin-stimulated ECM degradation and ferroptosis in mouse chondrocytes. METTL14 inhibited GPX4 gene through m6A methylation modification. GPX4 knockdown reversed the si-METTL14-mediated protection in IL-1ß-induced chondrocytes. CONCLUSION: METTL14 depletion inhibits ferroptosis and ECM degradation by suppressing GPX4 mRNA m6A modification in injured chondrocytes.

Alternate levels versus all levels mini-plate fixation in C3-6 cervical laminoplasty: a retrospective comparative study.

OBJECTIVE: The purpose of this study is to compare radiological and clinical outcomes between alternate levels (C4 and C6) and all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. METHODS: Ninety-six patients who underwent C3-6 unilateral open-door laminoplasty with alternate levels mini-plate fixation (54 patients in group A) or all levels mini-plate fixation (42 patients in group B) between September 2014 and September 2019 were reviewed in this study. Radiologic and clinical outcomes were assessed. Clinical results included Visual Analogue Scale (VAS) of axial neck pain and Japanese Orthopedic Association (JOA) score. Radiographic results included cervical range of motion (ROM), cervical curvature index (CCI), and the spinal canal expansive parameters including open angle, anteroposterior diameter (APD), and Pavlov`s ratio. RESULTS: There was no significant difference in VAS, JOA score, ROM, and CCI between two groups. There was no significant difference in canal expansion postoperatively between two groups. However, open angle, APD, and Pavlov`s ratio in group A decreased significantly during the follow-up. In group B, APD, Pavlov`s ratio, and open angle were maintained until the final follow-up. There was no hardware failure or lamina reclosure occurred in both groups during the follow-up. The mean cost of group B was higher than that of group A. CONCLUSIONS: Despite the differences in the maintenance of canal expansion, alternate levels mini-plate fixation can achieve similar clinical outcomes as all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. As evidenced in this study, we believe C3-6 laminoplasty with alternate levels (C4 and C6) mini-plate fixation is an economical, effective, and safe treatment method.

Gradient failure mechanism and control technology of deep roadways under the action of deviatoric stress field.

Deformation control of deep roadways is a major challenge for mine safety production. Taking a deep roadway with a burial depth of 965 m in a mine in North China as the engineering background, on-site investigation found that significant creep deformation occurred in the surrounding rock of the roadway. The original supporting U-shaped steel support failed due to insufficient supporting strength. The rock mass near the roadway experienced a transition from triaxial stress conditions to biaxial and even uniaxial stress states as a result of excavation and unloading, leading to a gradient stress distribution in the surrounding rock. From the perspective of the roadway's deviatoric stress field distribution, we investigated the gradient failure mechanism of the roadway and validated it through theoretical analysis and numerical simulations. The study found that the ratio of horizontal principal stress and vertical principal stress determines the distribution shape of the surrounding rock deviatoric stress field. The gradient distribution of the stress field in the roadway will cause time-related deformation of the roadway, which will lead to large deformation and failure of the roadway. Based on this, the control mechanism of roadway gradient failure was studied, and then a combined support technology of CFST supports with high bearing capacity was proposed.

Global synthesis on the response of soil microbial necromass carbon to climate-smart agriculture.

Climate-smart agriculture (CSA) supports the sustainability of crop production and food security, and benefiting soil carbon storage. Despite the critical importance of microorganisms in the carbon cycle, systematic investigations on the influence of CSA on soil microbial necromass carbon and its driving factors are still limited. We evaluated 472 observations from 73 peer-reviewed articles to show that, compared to conventional practice, CSA generally increased soil microbial necromass carbon concentrations by 18.24%. These benefits to soil microbial necromass carbon, as assessed by amino sugar biomarkers, are complex and influenced by a variety of soil, climatic, spatial, and biological factors. Changes in living microbial biomass are the most significant predictor of total, fungal, and bacterial necromass carbon affected by CSA; in 61.9%-67.3% of paired observations, the CSA measures simultaneously increased living microbial biomass and microbial necromass carbon. Land restoration and nutrient management therein largely promoted microbial necromass carbon storage, while cover crop has a minor effect. Additionally, the effects were directly influenced by elevation and mean annual temperature, and indirectly by soil texture and initial organic carbon content. In the optimal scenario, the potential global carbon accrual rate of CSA through microbial necromass is approximately 980 Mt C year-1, assuming organic amendment is included following conservation tillage and appropriate land restoration. In conclusion, our study suggests that increasing soil microbial necromass carbon through CSA provides a vital way of mitigating carbon loss. This emphasizes the invisible yet significant influence of soil microbial anabolic activity on global carbon dynamics.

Crucial role played by CK8+ cells in mediating alveolar injury remodeling for patients with COVID-19.

The high risk of SARS-CoV-2 infection and reinfection and the occurrence of post-acute pulmonary sequelae have highlighted the importance of understanding the mechanism underlying lung repair after injury. To address this concern, comparative and systematic analyses of SARS-CoV-2 infection in COVID-19 patients and animals were conducted. In the lungs of nine patients who died of COVID-19 and one recovered from COVID-19 but died of unrelated disease in early 2020, damage-related transient progenitor (DATP) cells expressing CK8 marker proliferated significantly. These CK8+ DATP cells were derived from bronchial CK5+ basal cells. However, they showed different cell fate toward differentiation into type I alveolar cells in the deceased and convalescent patients, respectively. By using a self-limiting hamster infection model mimicking the dynamic process of lung injury remodeling in mild COVID-19 patients, the accumulation and regression of CK8+ cell marker were found to be closely associated with the disease course. Finally, we examined the autopsied lungs of two patients who died of infection by the recent Omicron variant and found that they only exhibited mild pathological injury with no CK8+ cell proliferation. These results indicate a clear pulmonary cell remodeling route and suggest that CK8+ DATP cells play a primary role in mediating alveolar remodeling, highlighting their potential applications as diagnostic markers and therapeutic targets.

Ultrasound Microbubble-Stimulated miR-145-5p Inhibits Malignant Behaviors of Breast Cancer Cells by Targeting ACTG1.

ABSTRACT: Ultrasound-targeted microbubble destruction (UTMD) technology combines ultrasound with a variety of functional microbubble vectors to enhance the transfection and expression of target genes, and has become a promising noninvasive method for localized gene transfer, which is widely used in gene therapy for cancer. This research aimed to explore the role of UTMD-mediated miR-145-5p on breast cancer (BC) tumorigenesis and the underlying mechanisms. To achieve UTMD-mediated miR-145-5p overexpression, BC cells were cotransfected with microbubbles (MBs) and miR-145-5p mimics. The BC cell malignant phenotypes were assessed through CCK-8, wound healing, and transwell assays. MiR-145-5p and actin gamma 1 (ACTG1) binding relationship was verified through luciferase reporter and RNA pull-down assays. MiR-145-5p and ACTG1 levels in BC cells and tissues were detected through RT-qPCR and Western blotting. ACTG1 was upregulated, whereas miR-145-5p was downregulated in BC cells and tissues. MiR-145-5p targeted ACTG1 and negatively regulated its level in BC cells. Overexpressing miR-145-5p restrained BC cell growth, migration, and invasion. Ultrasound-targeted microbubble destruction improved the overexpression efficiency of miR-145-5p and enhanced the suppressive influence on BC cell malignant phenotypes. In addition, ACTG1 overexpression compromises the repression of UTMD-mediated miR-145-5p on cellular behaviors in BC. Ultrasound-targeted microbubble destruction-delivered miR-145-5p hindered malignant behaviors of BC cells through downregulating ACTG1.

Deep spatial proteomics reveals region-specific features of severe COVID-19-related pulmonary injury.

As a primary target of severe acute respiratory syndrome coronavirus 2, lung exhibits heterogeneous histopathological changes following infection. However, comprehensive insight into their protein basis with spatial resolution remains deficient, which hinders further understanding of coronavirus disease 2019 (COVID-19)-related pulmonary injury. Here, we generate a region-resolved proteomic atlas of hallmark pathological pulmonary structures by integrating histological examination, laser microdissection, and ultrasensitive proteomics. Over 10,000 proteins are quantified across 71 post-mortem specimens. We identify a spectrum of pathway dysregulations in alveolar epithelium, bronchial epithelium, and blood vessels compared with non-COVID-19 controls, providing evidence for transitional-state pneumocyte hyperplasia. Additionally, our data reveal the region-specific enrichment of functional markers in bronchiole mucus plugs, pulmonary fibrosis, airspace inflammation, and alveolar type 2 cells, uncovering their distinctive features. Furthermore, we detect increased protein expression associated with viral entry and inflammatory response across multiple regions, suggesting potential therapeutic targets. Collectively, this study provides a distinct perspective for deciphering COVID-19-caused pulmonary dysfunction by spatial proteomics.

Cardiogenic shock in a 28-year-old woman associated with sibutramine use.

A 28-year-old woman collapsed in her home, and her companion rushed to call emergency services. Upon arrival, a physician performed CPR and endotracheal intubation, successfully restoring her voluntary heart rhythm. However, while en route to the hospital, ventricular fibrillation recurred. Despite the restoration of her voluntary rhythm through electrical defibrillation, she remained in a comatose state, which eventually led to multiple organ failures. Family members revealed that she had a 2-month history of taking diet pills. Histological examination revealed cardiomyocyte necrosis, contraction band necrosis, interstitial hemorrhage, collagen deposition, interstitial fiber proliferation, and myofiber remodeling. Analysis of blood and urine using GC-MS and LC-MS detected sibutramine and its primary metabolites, M1 and M2, which were consistent with the composition of the medication she was taking. The deceased was in good health with no underlying heart disease. The above information confirmed that the cause of her death was sibutramine.

Update on the outcome of M-protein screening program of multiple myeloma in China: A 7-year cohort study.

BACKGROUND: To improve the early detection rate of multiple myeloma (MM), the M-protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based monoclonal immunoglobulin (M-protein) screening integrated into the blood biochemistry panel. This study updated 7-year follow-up findings of MM patients diagnosed by screening-driven and symptom-driven approaches. METHODS: The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening-driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma-related end-organ damage were categorized into the symptom-driven group. RESULTS: There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening-driven group, while 545 were to the symptom-driven group. Compared to the symptom-driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease-related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression-free survival (PFS) than the symptom-driven group (62.2 vs. 24.9 months, p < 0.001, HR: 2.12, 95% CIs: 1.69-2.65), with median follow-ups of 32.6 and 27.4 months. Furthermore, the median overall survival (OS) was significantly longer in patients of the screening group (not reached vs. 62.3 months, p < 0.001, HR: 2.49, 95% CIs: 1.81-3.41). After being adjusted for well-acknowledged myeloma prognostic factors, the screening-driven diagnostic pattern remained an independent prognostic factor indicating improved PFS and OS in MM patients. CONCLUSION: Routine M-protein screening for MM in the hospital population results in an earlier diagnosis and better patient outcomes.

Clinical profiles in multiple myeloma patients with extreme survivals: a study from a National Medical Center in China.

OBJECTIVES: The clinical outcomes of multiple myeloma (MM) patients are highly variable in the real-world setting. Some MM patients may have clinical endings that do not abide by the book. We aim to describe features of MM patients with extreme survivals in real-world practice. METHODS: This retrospective study enrolled 941 patients consecutively visited a national medical center, China, between July 1995 and December 2021. Among patients, we identified two groups of MM patients with extreme survivals, 56 were in the long-term remission (LR) group with progression-free survival (PFS) ≥ 60 months, and 82 were in the rapid progression (RP) group with PFS ≤ 6 months. RESULTS: CRAB features, of which hypercalcemia, renal insufficiency, and anemia were more common in the RP group, except for bone disease, with a comparable incidence at diagnosis in both groups (88.8 vs 85.7%, P = 0.52). High-risk cytogenetics was detected in 45.7% of patients in the RP group. Of note, 14.3% of MM patients in the LR group harbored del (17p). According to the Revised International Staging System (R-ISS), 9% of patients belonged to stage I in the RP group, and 19% of patients in the LR group were found in stage III. There were 8 (15.7%) patients in the LR group only achieved partial response (PR) as the best response. Median time to best response (TBR) for LR and RP group patients was 4.6 and 1.4 months, respectively. CONCLUSIONS: The disparities in the survivals of MM patients indicated that some unexpected factors have influenced the outcomes in the real-world setting.

Dimethyl sulfate poisoning in China: a fatal case and a 45-year retrospective study.

Dimethyl sulfate (DMS) is a highly toxic chemical that appears innocuous and is commonly used as a methylating agent in industry. It can be readily absorbed leading to poisoning or death through the skin or mucous membranes of the respiratory tract in the process of production or transportation. Although there are some articles on treatment for DMS poisoning, reports of death resulting from acute fatal DMS poisoning are very rare. Here, we present a case of a 50-year-old Chinese man who died accidentally from DMS poisoning after he broke a plastic storage tank full of DMS during transportation. The patient complained of eye irritation. In addition, the corrosive damage could be seen in his corneas and skin. The autopsy revealed erosions and ulcers in the respiratory tract, as well as massive congestion, necrosis, edema, and pseudomembrane formation on the mucous layer of the trachea and main bronchi. Histopathological examination confirmed extensive pulmonary edema, multifocal hemorrhages, whole-cell swelling in the brain, as well as disintegration of the neuronal cell. We inferred that DMS poisoning caused the symptoms resulting from the production of methanol and sulfate through hydrolysis, including respiratory toxicity and neurotoxicity, and these symptoms had temporal continuity. Toxicological analysis revealed no DMS or methanol, but formic acid was detected in the brain, both qualitatively and quantitatively. In this report, we also present a retrospective study of 8 similar cases of DMS poisoning in literature in China, including some clinical data and autopsy information.

The obesity paradox in multiple myeloma: A report from Multiple Myeloma Research Foundation (MMRF) dataset.

BACKGROUND: Obesity is a risk factor for multiple myeloma (MM). However, we still lack knowledge on the clinical course of obese MM patients in a broad view. METHODS: Here, we reviewed 568 MM patients recorded in the Multiple Myeloma Research Foundation (MMRF) coMMpass dataset. Patients were divided into the normal and obese groups according body mass index (BMI) at diagnosis, and then the baseline characteristics, cytogenetic abnormalities, treatment variability, and survival outcomes were evaluated in the obese cohort. RESULTS: We found no differences in the characteristics when comparing normal and obese MM patients other than more male in the obese part (50.4% vs. 59.9%, p = 0.024). Compared with the normal BMI patients, median overall survival (OS) was shorter for obese MM patients but without significant meaning (82.3 vs. 95.3 months, p = 0.25). However, in the subgroup analysis, obese MM patients younger than 65 years had significantly inferior OS than that in the normal category (p = 0.047). We also found obese MM patients had a higher overall response rate (ORR) compared with normal BMI patients (92.7% vs. 88.6%, p = 0.037). Additionally, obese patients seemed to achieve faster best response during first-line therapy. CONCLUSIONS: Obesity assumes a paradoxical function in the clinical trajectory of myeloma.

Cranial midline shift is a predictor of the clinical prognosis of acute cerebral infarction patients undergoing emergency endovascular treatment.

Endovascular treatment is widely used in acute cerebral infarction (ACI), but patient prognosis varies greatly. We aimed to investigate the predictive value of midline shift (MLS) threshold for the clinical prognosis of patients with ACI who undergo emergency endovascular treatment. We prospectively enrolled patients with ACI who received endovascular treatment within 24 h of onset. Cranial images were collected within 24 h after endovascular treatment. We assessed MLS at the level of the midbrain, pineal calcification, septum pellucida, and falx cerebri and noted the maximum MLS (MLS[max]) among these locations. Functional outcomes were assessed at 90 days using the modified Rankin Scale. Receiver operating characteristic curves and optimal cutoff points were used to analyze the predictive value of MLS. We enrolled 82 patients, including 46 with poor outcomes. Although the MLS values at all levels were significantly different between the poor and favorable outcome groups (p < 0.01), the MLS(max) tended to be a better marker for 90-day poor outcome. To predict poor outcome, the optimal cutoff values for MLS(max) within 24 and 48 h after intervention were 0.45 and 2.35 mm, respectively. MLS(max) has predictive value for patient prognosis.

Procedural Promotion of Multiple Stages in the Wound Healing Process by Graphene-Spiky Silica Heterostructured Nanoparticles.

Background: Multiple stages including hemostasis, inflammation, proliferation, and remodeling were involved in the wound healing process. The increase in nanomaterials in recent years has extended the scope of tools for wound healing; however, it is still difficult to achieve the four multistage procedures simultaneously. Materials and Methods: In this study, graphene-spiky silica heterostructured nanoparticles (GS) were synthesized for the procedural acceleration of the multistage in wound healing process. The nanobridge effect of GS was analyzed through the adhesion of two skins, the antibacterial effect was assessed in Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria, cell proliferation and migration were investigated in mouse embryonic fibroblast (NIH-3T3) cells, and the in vivo wound healing effect was examined in female BALB/c mice with a cutting wound and E. coli or S. aureus bacteria infection on the back. Results: First, GS has a strong nanobridge effect on the rapid closure of wounds because the spiky architecture on the surface of GS facilitates the adhesion of skins, promoting the hemostasis stage. Second, graphene exhibits antimicrobial activities both in chemical and physical interactions, especially under simulated sunlight irradiation. Third, graphene plays an important role in scaffolding function, together with the spiky topographical architecture of GS, accelerating the proliferation and maturation stages. Conclusion: By periodically promoting every stage of wound healing, GS combined with simulated sunlight irradiation could significantly accelerate wound healing. With a simple composition and compact structure but multiple functions, this strategy will be the guideline for the development of ideal wound-healing nanomaterials.

The causal relationship between autoimmune diseases and osteoporosis: a study based on Mendelian randomization.

Objective: The relationship between different autoimmune diseases and bone mineral density (BMD) and fractures has been reported in epidemiological studies. This study aimed to explore the causal relationship between autoimmune diseases and BMD, falls, and fractures using Mendelian randomization (MR). Methods: The instrumental variables were selected from the aggregated statistical data of these diseases from the largest genome-wide association study in Europe. Specifically, 12 common autoimmune diseases were selected as exposure. Outcome variables included BMD, falls, and fractures. Multiple analysis methods were utilized to comprehensively evaluate the causal relationship between autoimmune diseases and BMD, falls, and fractures. Additionally, sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and one analysis, were conducted to verify the result's reliability. Results: Strong evidence was provided in the results of the negatively association of ulcerative colitis (UC) with forearm BMD. UC also had a negatively association with the total body BMD, while inflammatory bowel disease (IBD) depicted a negatively association with the total body BMD at the age of 45-60 years. Horizontal pleiotropy or heterogeneity was not detected through sensitivity analysis, indicating that the causal estimation was reliable. Conclusion: This study shows a negative causal relationship between UC and forearm and total body BMD, and between IBD and total body BMD at the age of 45-60 years. These results should be considered in future research and when public health measures and osteoporosis prevention strategies are formulated.

An Open-Label, Uncontrolled, Single-Arm Clinical Trial of Tofacitinib, an Oral JAK1 and JAK3 Kinase Inhibitor, in Chinese Patients with Keloid.

BACKGROUND: The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated. OBJECTIVES: This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients. METHODS: We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro. RESULTS: After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway. CONCLUSION: Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.

Assessment of atmospheric heavy metal pollution in Qinghai-Tibet Plateau: Using mosses as biomonitor.

Atmospheric heavy metal (HM) pollution may pose a significant threat to the fragile ecosystem of Qinghai-Tibet Plateau (QTP). To investigate potential atmospheric HM pollution within the QTP region of China, mosses, along with other higher plants and soil, were collected from 33 sites for heavy metal measurement. The concentration ranges of Zn, Pb, Cd, and Cu in mosses were 6.07-69.9, 5.36-23.9, 0.60-1.05, and 14.4-50.5 mg·kg-1 (dry weight), respectively, significantly higher than those in other higher plants, except for Zn. The spatial distribution of relative concentrations (RCs; moss to top soil) of HMs varied considerably, indicating distinct differences in atmospheric Zn and Cu pollution levels between the northern and southern QTP. This study first reported that moderate regional atmospheric Cu pollution, primarily due to large-scale mining in recent years, had occurred, particularly in southern QTP. Pb also presented slight pollution due to anthropogenic activities. However, Cd showed almost no atmospheric pollution, while Zn concentrations were relatively high in southern QTP. Although less severe than atmospheric pollution levels in Chinese inland or coastal cities, the atmospheric pollution of Pb and Cu in QTP indicated by mosses were far more severe than global background areas, or even worse than most European cities.

Serum levels of type I interferon (IFN-I) is associated with the severity of COVID-19.

Introduction. Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, coronavirus disease 2019 (COVID-19) has threatened global public health. Immune damage mechanisms are essential guidelines for clinical treatment and immune prevention.Hypothesis. The dysregulated type I interferon (IFN-I) responses, lymphocytopenia and hypercytokinemia during SARS-CoV-2 infection have been reported. However, whether there is a correlation between levels of IFN-I and the severity of COVID-19 has not been reported yet.Aim. To investigate the source of IFN-I and detect the exact roles of them in the pathogenesis of COVID-19.Methodology. Here ELISA was used to detect serum IFN-I (IFN-α and IFN-ß) for 137 cases with laboratory-confirmed COVID-19 admitted into one hospital in Wuhan from December 2019 to March 2020, and the relationships between IFN-α/ß concentrations and patients' clinical parameters were conducted by statistical analysis.Results. Both IFN-α and IFN-ß concentrations dramatically increased in COVID-19 patients, especially in old patients (>80 years) and severe cases. Statistical analysis demonstrated that serum IFN-α/ß concentrations were negatively correlated with the counts of total CD3+T, CD4+ and CD8+T cells, especially in critically ill cases. Moreover, serum IFN-α levels were positively correlated to IL-6 and TNF-α. Finally, immunofluorescent double staining showed that IFN-α and IFN-ß are major secretions from macrophages and dendritic cells (DCs) in lymph nodes from COVID-19 autopsies.Conclusion. These results demonstrate that macrophages and DCs are the main origination of IFN-I, and serum levels of IFN-I are positively associated with lymphopenia and cytokine storm, suggesting that IFN-α/ß deteriorated the severity of COVID-19. Anti-interferon or IFN-I signalling block drugs are needed to treat ICU patients.

Periodontal Status and Saliva Metabolic Signature in Patients with Alzheimer's Disease.

BACKGROUND: Characterizing the periodontal status of patients with Alzheimer's disease (AD), investigating differences in salivary metabolism between patients with and without AD under the same periodontal conditions, and understanding how it is related to oral flora are critical. OBJECTIVE: We aimed to examine the periodontal condition of patients with AD and to screen salivary metabolic biomarkers from the saliva of individuals with and without AD with matched periodontal conditions. Furthermore, we aimed to explore the possible relationship between salivary metabolic changes and oral flora. METHODS: In total, 79 individuals were recruited into the experiment for periodontal analysis. Especially, 30 saliva samples from the AD group and 30 from healthy controls (HCs) with matched periodontal conditions were selected for metabolomic analysis. The random-forest algorithm was used to detect candidate biomarkers. Among these, 19 AD saliva and 19 HC samples were selected to investigate the microbiological factors influencing the alterations in saliva metabolism in patients with AD. RESULTS: The plaque index and bleeding on probing were considerably higher in the AD group. Further, Cis-3-(1-carboxy-ethyl)-3,5-cyclohexadiene-1,2-diol, dodecanoic acid, genipic acid, and N, N-dimethylthanolamine N-oxide were determined as candidate biomarkers, based on the area under the curve (AUC) value (AUC = 0.95). The results of oral-flora sequencing showed that dysbacteriosis may be a reason for the differences in AD saliva metabolism. CONCLUSION: Dysregulation of the proportion of specific bacterial flora in saliva plays a vital role in metabolic changes in AD. These results will contribute to further improving the AD saliva biomarker system.