Using Data-Driven Methods and Aging Information to Quantitatively Identify Microplastic Environmental Sources and Establish a Comprehensive Discrimination Index.

The global distribution of microplastics (MPs) across various environmental compartments has garnered significant attention. However, the differences in the characteristics of MPs in different environments remain unclear, and there is still a lack of quantitative analysis of their environmental sources. In addition, the inclusion of aging in source apportionment is a novel approach that has not been widely explored. In this study, we conducted a meta-analysis of the literature from the past 10 years and extracted conventional and aging characteristic data of MPs from 321 sampling points across 7 environmental compartments worldwide. We established a data-driven analysis framework using these data sets to identify different MP communities across environmental compartments, screen key MP features, and develop an environmental source analysis model for MPs. Our results indicate significant differences in the characteristics of MP communities across environments. The key features of differentiation were identified using the LEfSe method and include the carbonyl index, hydroxyl index, fouling index, proportions of polypropylene, white, black/gray, and film/sheet. These features were screened for each environmental compartment. An environmental source identification model was established based on these features with an accuracy of 75.1%. In order to accurately represent the single/multisource case in a more probabilistic manner, we proposed the MP environmental source index (MESI) to provide a probability estimation of the sample having multiple sources. Our findings contribute to a better understanding of MP migration trends and fluxes in the plastic cycle and inform effective prevention and control strategies for MP pollution.

Phototheranostic Metal-Phenolic Networks with Antiexosomal PD-L1 Enhanced Ferroptosis for Synergistic Immunotherapy.

Tumor-derived exosome can suppress dendritic cells (DCs) and T cells functions. Excessive secretion of exosomal programmed death-ligand 1 (PD-L1) results in therapeutic resistance to PD-1/PD-L1 immunotherapy and clinical failure. Restored T cells by antiexosomal PD-L1 tactic can intensify ferroptosis of tumor cells and vice versa. Diminishing exosomal suppression and establishing a nexus of antiexosomal PD-L1 and ferroptosis may rescue the discouraging antitumor immunity. Here, we engineered phototheranostic metal-phenolic networks (PFG MPNs) by an assembly of semiconductor polymers encapsulating ferroptosis inducer (Fe3+) and exosome inhibitor (GW4869). The PFG MPNs elicited superior near-infrared II fluorescence/photoacoustic imaging tracking performance for a precise photothermal therapy (PTT). PTT-augmented immunogenic cell death relieved exosomal silencing on DC maturation. GW4869 mediated PD-L1 based exosomal inhibition revitalized T cells and enhanced the ferroptosis. This novel synergy of PTT with antiexosomal PD-L1 enhanced ferroptosis evoked potent antitumor immunity in B16F10 tumors and immunological memory against metastatic tumors in lymph nodes.

A Metal-Phenolic Nanosensitizer Performs Hydrogen Sulfide-Reprogrammed Oxygen Metabolism for Cancer Radiotherapy Intensification and Immunogenicity.

Radiotherapy (RT) is hampered by the limited oxygen in tumors, which could be potentiated via reprogramming the oxygen metabolism and increasing the oxygen utilization efficiency. Herein, a metal-phenolic nanosensitizer (Hf-PSP-DTC@PLX) was integrated via an acid-sensitive hydrogen sulfide (H2 S) donor (polyethylene glycol-co-polydithiocarbamates, PEG-DTC) and a hafnium-chelated polyphenolic semiconducting polymer (Hf-PSP) in an amphiphilic polymer (poloxamer F127, PLX). Hf-PSP-DTC@PLX elicited a high imaging performance for precise RT and generated H2 S to reduce the cellular oxygen consumption rate via mitochondrial respiration inhibition, which reprogrammed the oxygen metabolism for improvement of the tumor oxygenation. Then, Hf-sensitization could fully utilize the well-preserved oxygen to intensify RT efficacy and activate immunogenicity. Such a synergistic strategy for improvement of oxygenation and oxygen utilization would have great potential in optimizing oxygen-dependent therapeutics.

Nanostructure of Functional Larotaxel Liposomes Decorated with Guanine-Rich Quadruplex Nucleotide-Lipid Derivative for Treatment of Resistant Breast Cancer.

Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine-rich quadruplex nucleotide-lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer-bearing mice. The nucleotide-lipid derivative (DSPE-PEG2000 -C6 -GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT-28nt (containing 17 guanines and 11 thymidines) and DSPE-PEG2000 -NHS, and is incorporated on the functional larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer-bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK-STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional larotaxel liposomes can be used for effective treatment of drug-resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide-lipid derivative.

Effects of microplastics (MPs) and tributyltin (TBT) alone and in combination on bile acids and gut microbiota crosstalk in mice.

Microplastics (MPs) and tributyltin (TBT) are both potential environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both pollutants) on mammals remain unclear. In this study, Ф5µm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced inflammation in the liver, altered gut microbiota composition and disturbed fecal bile acids profiles. In addition to decreasing triglyceride (TG) and increasing aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic cholestasis by stimulating the expression of the cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and bile-salt export pump (BSEP) to prevent bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased 7-ketolithocholic acid (7-ketoLCA) and taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased interferon γ (IFNγ) and Mpeg1 levels to induce inflammation, accompanied by decreased 7-ketoLCA, tauro-alpha-muricholic acid (T-alpha-MCA) and alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome dysbiosis and subsequently alter bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.

Association between COX2 -765G/C polymorphism and periodontitis in Chinese population: a meta-analysis.

BACKGROUND: Studies had attempted to clarify the relation between COX2 -765G/C gene polymorphisms and periodontitis risk, but there has been no definite consensus to date. A meta-analysis was performed to further explore the relationship of COX2 -765G/C polymorphism on periodontitis risk among Chinese population. METHODS: The databases of PubMed, Springer Link, Ovid, Chinese Wanfang Databases, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biology Medicine were searched up to January 2017. The overall result and subgroup analysis results were combined using fixed-effect or random-effect based on the heterogeneity. RESULTS: Finally, 7 case-control publications including 1399 periodontitis cases and 1663 controls were identified according to the inclusion criteria. In the total analyses, COX2 -765G/C polymorphism had nonsignificant association on periodontitis risk in all models. The subgroup analyses suggested a significantly increased risk of periodontitis in studies with population-based controls and a significantly decreased risk in studies with hospital-based controls. CONCLUSIONS: This meta-analysis indicated that COX2 -765G/C polymorphism had significantly affect on periodontitis risk among Chinese individuals, which should be confirmed by other ethnic groups.

Self-Assembled Pyridine-Dipyrrolate Cages.

An inherently nonlinear pyridine dipyrrolate ligand, namely 2,6-bis(3,4-diethyl-5-carboxy-1H-pyrrol-2yl)pyridine (compound 1), is able to distinguish between different zinc(II) cation sources, namely Zn(acac)2 and Zn(OAc)2, respectively. This differentiation is manifest both in terms of the observed fluorescent behavior in mixed organic media and the reaction chemistry. Treatment of 1 with Zn(acac)2 gives rise to a cage dimer, cage-1, wherein two molecules of compound 1 act as double bridging units to connect two individual cage subunits. As inferred from X-ray crystallographic studies, this cage system consists of discrete zinc dimers with hydroxide bridges that, with the assistance of bound DMF solvent molecules, serve to fix the geometry and orientation of the pyridine dipyrrolate building blocks. When a different zinc source, Zn(OAc)2, is used to carry out an ostensibly similar complexation reaction with compound 1, an acetate-bridged 1D abacus-like cage polymer is obtained as inferred from X-ray diffraction analysis. This extended solid state structure, cage-2, contains individual zinc dimer cage submits and appears stabilized by solvent molecules (DMF) and the counteranion (acetate). Rod-like assemblies are also observed by DLS and SEM. This construct, in contrast to cage-1, proved fluorescent in mixed organic media. The structure of the ligand itself (i.e., in the absence of Zn(II)) was confirmed by X-ray crystallographic analysis and was found to assemble into a supramolecular polymer. Conversion to a dimer form was seen upon the addition of TBAOAc. On the basis of the metric parameters, the structures seen in the solid state are stabilized via hydrogen bonding interactions involving solvent molecules.

[Study on the acid hydrolysis, fiber remodeling and bionics mineralization of rat tail tendon collagen type â ].

Objective: To produce bionic bone material that is consistent with human bone in chemical composition and molecular structure using rat tail tendon collagen type Ⅰ. Methods: The type Ⅰcollagen derived from rat tail was extracted by acetic acid to form collagen fibers. The reconstructed collagen fibers were placed in the mineralized solution to mimic bone mineralization for 2-6 days. Bone mineralization was observed by transmission electron microscopy and electron diffraction.Results: Collagen fibers with characteristic D-Band structure were reconstructed by using rat tail tendon collagen type Ⅰ extracted with acid hydrolysis method. Transmission electron microscopy and electron diffraction showed that calcium hydroxyapatite precursor infiltrated into the collagen fibers, and the collagen fibers were partially mineralized after 2 days of mineralization; the collagen fibers were completely mineralized and bionic bone material of typeⅠ collagen/calcium hydroxyapatite was formed after 6 days of mineralization.Conclusion: The collagen type Ⅰ can be extracted from rat tail tendon by acid hydrolysis method, and can be reformed and mineralized to form the bionic bone material which mimics human bone in chemical composition and the molecular structure.

Combined influence of the nanoplastics and polycyclic aromatic hydrocarbons exposure on microbial community in seawater environment.

Nanoplastics (NPs) and polycyclic aromatic hydrocarbons (PAHs) are recognized as persistent organic pollutant (POPs) with demonstrated physiological toxicity. When present in aquatic environments, the two pollutants could combine with each other, resulting in cumulative toxicity to organisms. However, the combined impact of NPs and PAHs on microorganisms in seawater is not well understood. In this study, we conducted an exposure experiment to investigate the individual and synergistic effects of NPs and PAHs on the composition, biodiversity, co-occurrence networks of microbial communities in seawater. Exposure of individuals to PAHs led to a reduction in microbial community richness, but an increase in the relative abundance of species linked to PAHs degradation. These PAHs-degradation bacteria acting as keystone species, maintained a microbial network complexity similar to that of the control treatment. Exposure to individual NPs resulted in a reduction in the complexity of microbial networks. Furthermore, when PAHs and NPs were simultaneously present, the toxic effect of NPs hindered the presence of keystone species involved in PAHs degradation, subsequently limiting the degradation of PAHs by marine microorganisms, resulting in a decrease in community diversity and symbiotic network complexity. This situation potentially poses a heightened threat to the ecological stability of marine ecosystems. Our work strengthened the understanding of the combined impact of NPs and PAHs on microorganisms in seawater.

Optimization of parameters for preparation of docetaxel-loaded PLGA nanoparticles by nanoprecipitation method.

The purpose of this study was to develop docetaxel-poly (lactide-co-glycolide) (PLGA) loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows: the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate (TPGS) was 0.2%, the ratio of oil phase to water phase was 1:5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was (40.83±2.1)%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere® and play great roles in future.

[Application of vancomycin-loaded calcium sulphate in treatment of osteomyelitis].

OBJECTIVE: To investigate the role of vancomycin-loaded calcium sulphate in the treatment of osteomyelitis. METHODS: We implanted vancomycin-loaded calcium sulphate into 24 patients with traumatic osteomyelitis who were treated in our hospital from February 2008 to February 2010,and then the antibiotic concentrations in the lesions were measured.Bacterial culture results,inflammatory markers,as well as wound healing were observed.X-ray was performed in the location where the vancomycin-loaded calcium sulphate was implanted.The blood vancomycin level as well as liver and kidney functions were determined. RESULTS: The vancomycin concentration in the lesion exceeded the effective therapeutic concentrations and the minimum inhibitory concentration,while the blood concentration was low.The liver and renal function remained normal.The safety profile was good,and the cure rate of osteomyelitis reached 100%. CONCLUSIONS: The vancomycin-loaded calcium sulphate can release high-concentration vancomycin in the diseased sites without causing high blood concentration.Also,it can guide the regeneration of bones.Therefore,it is effective and safe in treating osteomyelitis.

Case Report: Report of Infective Endocarditis Caused by Abiotrophia defectiva and Literature Review.

Objective: To report the clinical features of the first child with infective endocarditis (IE) caused by Abiotrophia defectiva in mainland China and to raise awareness of the disease. Methods: The clinical data of a child with IE caused by A. defectiva admitted to Xi'an Children's Hospital in July 2021 were collected, and the relevant literature was reviewed. Results: The child was a female, 8 years old, admitted with fever for 4 days and right-sided limb weakness for 3 days. The illness started with suppurative tonsillitis, followed by headache, fatigue, right-sided mouth, slurred speech, right limb weakness, and unstable holding. Transthoracic echocardiography showed that the mitral valve vegetation was formed and vegetation could also be seen at the entrance of the pulmonary vein at the posterior wall of the left atrium. Cranial contrast-enhanced MRI + magnetic resonance angiography showed multiple intracranial pseudoaneurysm formation and pontine infarction. After A. defectiva was detected by metagenomic next-generation sequencing (mNGS) in cerebrospinal fluid and blood detected, the infection was controlled by anti-infective treatment with meropenem and vancomycin. On the 36th day after admission, due to severe headache and slurred speech, the head CT showed hemorrhage of right parietal pseudoaneurysm and cerebral sickle hernia, and right temporo-occipital hematoma evacuation, cerebrovascular malformation resection, and cranial decompression were performed immediately. After the surgery, her speech ability gradually recovered, the muscle strength of her left upper limb was about grade III, while the muscle strength of the rest of the limbs was normal. After a total of 60 days of hospitalization, her family requested to be discharged. Conclusion: This pediatric patient is the first case of childhood IE caused by A. defectiva in mainland China, and the first time in the world that A. defectiva was detected by mNGS in patients with IE.

Effects of microplastics on the accumulation and neurotoxicity of methylmercury in zebrafish larvae.

Microplastics (MPs) and methylmercury (MeHg) have attracted increasing attention due to ubiquitous occurrence and toxicity. This study aimed to investigate whether MPs could absorb MeHg and thus modify its bioconcentration and neurotoxicity in the zebrafish larvae (Danio rerio). The pseudo-second-order model (R2 = 0.989) was found to be suitable for describing the adsorption kinetics of MeHg onto MPs. Compared with Freundlich and Temkin models, the Langmuir isotherm model provided a better fit with the experimental data exhibiting a maximum monolayer adsorption capacity of 54.945 mg/g. These results suggested that adsorption occurs mainly by a chemical process dominated by monolayer adsorption. MPs adsorbed MeHg to form MPs/MeHg complex, which was ingested by zebrafish larvae, and promoted accumulation of MeHg. Thus, the presence of MPs aggravated the reduction of locomotor activity induced by MeHg, and downregulation of neurotransmitters related genes, such as ache, gfap and scl1A3b. Metabolome analysis also revealed disrupted glutathione (GSH) metabolism upon exposure of MeHg alone and in combination with MPs, as reflected by the increased in the ratio of GSH and oxidized glutathione. These effects were also confirmed by upregulation of oxidative stress-related genes, such as sod, sod mt and gpx4a. Collectively, these results indicated that MPs could act as a carrier of MeHg and enhance its accumulation in zebrafish, thereby disrupting locomotor activity by excessive oxidative stress. This study provides a scientific basis for improving health risk assessment of environmental pollutants, particularly those potentially able to adsorb to MPs by virtue of their chemical nature.

[Treatment of severe medial tibial bone defect in primary total knee arthroplasty with autogenous bone graft and plate fixation].

OBJECTIVE: To explore the technique of autogenous bone graft combined with plate fixation in total knee arthroplasty(TKA) with severe proximal medial tibial bone defect. METHODS: From March 2012 to October 2018, 21 patients (9 males and 12 females) with severe bone defects in the proximal medial tibia during primary total knee arthroplasty were treated with autogenous structural bone grafting and steel plate fixation, with an age of 61 to 77 years old with an average of (69.6±9.1) years and a course of 64 to 257 months with an average of (73.6±170.7) months. According to Rand classification, there were 13 cases of type Ⅲb and 8 cases of type Ⅳb. Postoperative complications were observed, and knee joint function was evaluated by the Hospital for Special Surgery (HSS) score and SF-36 quality of life score. RESULTS: All 21 patients were followed up for 37 to 64 months with an average of (49.5±13.7) months. The incisions of all patients healed smoothly, and 2 patients developed lower limb intermuscular venous plexus thrombosis after operation. There were no periprosthetic infection, loosening of prosthesis and other complications. The autogenous bone grafts of all patients achieved bony healing during postoperative X-ray follow-up, and the healing time was 8 to 13 months with an average of (10.1±2.3) months. The HSS score of patients increased significantly from 30 to 48 with an average of (53.4±4.2) before operation to 75 to 92 with an average of (81.2±8.4) at the final follow-up (P<0.05). The SF-36 quality of life score of patients after operation was significantly different from that before operation (P<0.05). CONCLUSION: The technique of autogenous bone graft combined with steel plate fixation can achieve satisfactory osseointegration effect in the treatment of severe proximal tibial bone defects in primary knee arthroplasty, with less complications and obvious improvement in knee function.

[Value of quantitative CT in vertebroplasty for osteoporotic fracture combined with scoliosis].

OBJECTIVE: To investigate the value of lumbar quantitative CT (QCT) in vertebroplasty for osteoporotic fracture combined with scoliosis. METHODS: The clinical data of 60 patients with osteoporotic fractures combined with different degrees of scoliosis treated by vertebroplasty from December 2017 to December 2019 were retrospectively analyzed. There were 18 males and 42 females, aged from 65 to 81 (72.63±3.34)years old. All patients were received QCT examination before surgery. According to the QCT value, the patients were divided into osteopenia group(QCT>80 g/L, 10 cases, 12 vertebrae), osteoporosis group(QCT 40-80 g/L, 35 cases, 48 vertebrae) and severe osteoporosis group(QCT<40 g/L, 15 cases, 22 vertebrae). The dispersion and leakage of bone cement in the injured vertebrae of patients with different degrees of QCT value were observed, and the QCT value in the selection of puncture point, correction of Cobb angle and recovery of vertebral height were analyzed in the patients. RESULTS: Among 60 cases of 82 vertebrae, 41 cases of 55 vertebrae were punctured by concave unilateral puncture, according for 67.07%. Among them, there were 2 cases with 2 vertebrae in osteopenia group, 26 cases with 35 vertebrae in osteoporosis group, and 13 cases with 18 vertebrae in severe osteoporosis group. There was significant difference in the number of cases with unilateral or bilateral puncture among the three groups (χ2=13.699, P=0.001); there was no significant difference in the number of cases with bone cement leakage among the three groups (χ2=1.403, P=0.496). The Cobb angle of scoliosis was significantly differentbetween preoperative and postoperative follow-up(P<0.05);the height of injured vertebral body was significantly different between preoperative and postoperative follow-up (P<0.05). CONCLUSION: For patients with osteoporotic fracture combined with scoliosis undergoing vertebroplasty, the severity of osteoporosis should be determined according to lumbar QCT detection, and the concave side of scoliosis should be selected for puncture, which is conducive to improving scoliosis, restoring spinal stability and improving surgical safety.

A metal-polyphenolic nanosystem with NIR-II fluorescence-guided combined photothermal therapy and radiotherapy.

Photothermal therapy (PTT) achieves substantive therapeutic progress in certain tumor types without exogenous agents but is hampered by the over-activated inflammatory response or tumor recurrence in some cases. Herein, we technically developed the metal-polyphenolic nanosystem with precise NIR-II fluorescence-imaging guidance for combining hafnium (Hf)-sensitized radiotherapy with PTT to regress tumor growth.

Corrosion behavior of an AZ91D magnesium alloy under a heterogeneous electrolyte layer.

The corrosion behavior of an AZ91D magnesium alloy was investigated under a heterogeneous electrolyte layer by using electrochemical methods and surface analysis techniques. Dynamic polarization curves and morphological characterization were obtained at the center and near the edge zones under the electrolyte layer. The influence of the gas/liquid/solid three-phase boundary zone (TPB) on the corrosion behavior of the AZ91D magnesium alloy was discussed. The corrosion rate changed more significantly near the TPB zone than that at the other zones. The AZ91D alloy exhibited the characteristics of filiform corrosion together with shallow pitting corrosion. Different from the randomly distributed shallow pits, the filiform corrosion preferred to initiate near the TPB region and then progressively expanded adjacent to the edge of the electrolyte layer. The TPB zone played a vital role in determining the corrosion location, the corrosion morphologies and the corrosion rate of the magnesium alloy by influencing the mass transport process of carbon dioxide.

In Vivo Glutamate Sensing inside the Mouse Brain with Perovskite Nickelate-Nafion Heterostructures.

Glutamate, one of the main neurotransmitters in the brain, plays a critical role in communication between neurons, neuronal development, and various neurological disorders. Extracellular measurement of neurotransmitters such as glutamate in the brain is important for understanding these processes and developing a new generation of brain-machine interfaces. Here, we demonstrate the use of a perovskite nickelate-Nafion heterostructure as a promising glutamate sensor with a low detection limit of 16 nM and a response time of 1.2 s via amperometric sensing. We have designed and successfully tested novel perovskite nickelate-Nafion electrodes for recording of glutamate release ex vivo in electrically stimulated brain slices and in vivo from the primary visual cortex (V1) of awake mice exposed to visual stimuli. These results demonstrate the potential of perovskite nickelates as sensing media for brain-machine interfaces.

Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II).

OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. INCLUSION CRITERIA: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1)Adults aged 18-65 years;2)Voluntarily participate in this clinical trial and sign the "informed consent form" or have consent from a legal representative.3)Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg).4)COVID-19 featured lung lesions in chest X-ray image. EXCLUSION CRITERIA: Patients will be excluded from the study if they meet any of the following criteria. 1.Patients have received other experimental treatment for COVID-19 within the last 30 days;2.Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);3.Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;4.Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;5.Female patients who have no sexual protection in the last 30 days prior to the screening assessment;6.Pregnant or lactating women or women using estrogen contraception;7.Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;8.Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x107 human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: GradeDescriptionGrade 1:Discharged of patient;Grade 2:Hospitalized without oxygen supplement;Grade 3:Hospitalized, oxygen supplement is required, but NIV / HFNC is not required;Grade 4:Hospitalized in intensive care unit, and NIV / HFNC treatment is required;Grade 5:Hospitalized in intensive care unit, requiring ECMO and/or IMV;Grade 6:Death. ABBREVIATIONS: NIV, non-invasive mechanical ventilation; HFNC, high-flow nasal catheter; IMV, invasive mechanical ventilation. 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h ± 30min, 24h ± 30min after the injection) and follow-up period D90 ± 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h ± 30min, 24h ± 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 ± 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 ± 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 ß, IL-2, TNF-a, ITN-γ), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood ß-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 ± 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h ± 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient's randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16th April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Bacterial cellulose production by Acetobacter xylinum ATCC 23767 using tobacco waste extract as culture medium.

In this study, bacterial cellulose (BC) was synthesized by Acetobacter xylinum ATCC 23767 using tobacco waste extract (TWE) as a carbon source. Nicotine was found to be an inhibitory factor for BC synthesis, but it can be removed at pH 9.0 by steam distillation. After removing nicotine, the BC production was 2.27 g/L in TWE prepared with solid-liquid (S-L) ratio at 1:10. To further enhance the BC production, two fermentation stages were performed over 16 days by re-adjusting the pH to 6.5 at 7 days, after the first fermentation stage was completed. Using this two-stage fermentation, the BC production could reach 5.2 g/L. Structural and thermal analysis by FE-SEM, FT-IR, XRD and TGA showed the properties of BC obtained from TWE were similar to that from Hestrin-Schramm (HS) medium. Considering the huge disposal tobacco waste in China, the present study provides an alternative methodology to synthesize BC.