Mediating Triple Ions Migration Behavior via a Fluorinated Separator Interface toward Highly Reversible Aqueous Zn Batteries.

Rampant dendrite growth, electrode passivation and severe corrosion originate from the uncontrolled ions migration behavior of Zn2+ , SO4 2- , and H+ , which are largely compromising the aqueous zinc ion batteries (AZIBs) performance. Exploring the ultimate strategy to eliminate all the Zn anode issues is challenging but urgent at present. Herein, a fluorinated separator interface (PVDF@GF) is constructed simply by grafting the polyvinylidene difluoride (PVDF) on the GF surface to realize high-performance AZIBs. Experimental and theoretical studies reveal that the strong interaction between C─F bonds in the PVDF and Zn2+ ions enables evenly redistributed Zn2+ ions concentration at the electrode interface and accelerates the Zn transportation kinetics, leading to homogeneous and fast Zn deposition. Furthermore, the electronegative separator interface can spontaneously repel the SO4 2- and anchor H+ ions to alleviate the passivation and corrosion. Accordingly, the Zn|Zn symmetric cell with PVDF@GF harvests a superior cycling stability of 500 h at 10 mAh cm-2 , and the Zn|VOX full cell delivers 76.8% capacity retention after 1000 cycles at 2 A g-1 . This work offers an all-round solution and provides new insights for the design of advanced separators with ionic sieve function toward stable and reversible Zn metal anode chemistry.

Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration.

BACKGROUND: The use of gene therapy to deliver microRNAs (miRNAs) has gradually translated to preclinical application for the treatment of intervertebral disc degeneration (IDD). However, the effects of miRNAs are hindered by the short half-life time and the poor cellular uptake, owing to the lack of efficient delivery systems. Here, we investigated nucleus pulposus cell (NPC) specific aptamer-decorated polymeric nanoparticles that can load miR-150-5p for IDD treatment. METHODS: The role of miR-150-5p during disc development and degeneration was examined by miR-150-5p knockout (KO) mice. Histological analysis was undertaken in disc specimens. The functional mechanism of miR-150-5p in IDD development was investigated by qRT-PCR assay, Western blot, coimmunoprecipitation and immunofluorescence. NPC specific aptamer-decorated nanoparticles was designed, and its penetration, stability and safety were evaluated. IDD progression was assessed by radiological analysis including X-ray and MRI, after the annulus fibrosus needle puncture surgery with miR-150-5p manipulation by intradiscal injection of nanoparticles. The investigations into the interaction between aptamer and receptor were conducted using mass spectrometry, molecular docking and molecular dynamics simulations. RESULTS: We investigated NPC-specific aptamer-decorated polymeric nanoparticles that can bind to miR-150-5p for IDD treatment. Furthermore, we detected that nanoparticle-loaded miR-150-5p inhibitors alleviated NPC senescence in vitro, and the effects of the nanoparticles were sustained for more than 3 months in vivo. The microenvironment of NPCs improves the endo/lysosomal escape of miRNAs, greatly inhibiting the secretion of senescence-associated factors and the subsequent degeneration of NPCs. Importantly, nanoparticles delivering miR-150-5p inhibitors attenuated needle puncture-induced IDD in mouse models by targeting FBXW11 and inhibiting TAK1 ubiquitination, resulting in the downregulation of NF-kB signaling pathway activity. CONCLUSIONS: NPC-targeting nanoparticles delivering miR-150-5p show favorable therapeutic efficacy and safety and may constitute a promising treatment for IDD.

A Nature-Inspired Separator with Water-Confined and Kinetics-Boosted Effects for Sustainable and High-Utilization Zn Metal Batteries.

Uncontrollable dendrite growth and sluggish ion-transport kinetics are considered as the main obstacles for the further development of high-performance aqueous zinc ion batteries (AZIBs). Here, a nature-inspired separator (ZnHAP/BC) is developed to tackle these issues via the hybridization of the biomass-derived bacterial cellulose (BC) network and nano-hydroxyapatite particles (HAP). The as-prepared ZnHAP/BC separator not only regulates the desolvation process of the hydrated Zn2+ ions (Zn(H2 O)6 2+ ) by suppressing the water reactivity through the surface functional groups, alleviating the water-induced side-reactions, but also boosts the ion-transport kinetics and homogenize the Zn2+ flux, resulting in a fast and uniform Zn deposition. Remarkably, the Zn|Zn symmetric cell with ZnHAP/BC separator harvests a long-term stability over 1600 h at 1 mA cm-2 , 1 mAh cm-2 and endures stable cycling over 1025 and 611 h even at a high depth of discharge (DOD) of 50% and 80%, respectively. The Zn|V2 O5 full cell with a low negative/positive (N/P) capacity ratio of 2.7 achieves a superior capacity retention of 82% after 2500 cycles at 10 A g-1 . Furthermore, the Zn/HAP separator can be totally degraded within 2 weeks. This work develops a novel nature-derived separator and provides insights in constructing functional separators toward sustainable and advanced AZIBs.

Identification of TCR repertoires in asymptomatic COVID-19 patients by single-cell T-cell receptor sequencing.

The T cell-mediated immune responses associated with asymptomatic infection (AS) of SARS-CoV-2 remain largely unknown. The diversity of T-cell receptor (TCR) repertoire is essential for generating effective immunity against viral infections in T cell response. Here, we performed the single-cell TCR sequencing of the PBMC samples from five AS subjects, 33 symptomatic COVID-19 patients and eleven healthy controls to investigate the size and the diversity of TCR repertoire. We subsequently analyzed the TCR repertoire diversity, the V and J gene segment deference, and the dominant combination of αß VJ gene pairing among these three study groups. Notably, we revealed significant TCR preference in the AS group, including the skewed usage of TRAV1-2-J33-TRBV6-4-J2-2 and TRAV1-2-J33-TRBV6-1-J2-3. Our findings may shed new light on understanding the immunopathogenesis of COVID-19 and help identify optimal TCRs for development of novel therapeutic strategies against SARS-CoV-2 infection.

Malignant phosphaturic mesenchymal tumor-ossifying fibroma-like subtype: a case report and literature review.

BACKGROUND: A phosphaturic mesenchymal tumor (PMT) is classified into four histological subtypes: mixed connective tissue, osteoblast-like, non-ossifying fibroma-like, and ossifying fibroma-like. The ossifying fibroma-like subtype being extremely rare. Most PMTs are benign, with a minimal number becoming malignant after recurrence. In this study, we report a case of recurrence and malignant transformation of PMT-ossifying fibroma-like subtype in the left hip bone. CASE PRESENTATION: Here, we report the clinical manifestations, histology, pathological features, and treatment of a 57-year-old Chinese woman with a recurrent and malignant ossifying fibroma-like subtype PMT of the left iliac bone. The tumor was first discovered 3 years ago when the patient underwent surgery to remove the tumor. Precisely 2 years and 6 months after the operation, the pain in the left hip reappeared. After 6 months, the patient went to our hospital for treatment. After the tumor resection, the postoperative symptoms improved significantly, and the serum alkaline phosphatase level returned to normal. Based on clinical manifestations, evaluation of serum biochemical indicators, X-ray examination, computerized tomography scan of the pelvis, and histopathological examination of the two operations, the patient was finally diagnosed with a recurring and malignant transformation of the left iliac bone phosphaturic mesenchymal tumor-ossifying fibroma-like subtype. No tumor recurrence was found during the follow-up 15 months after the operation. CONCLUSIONS: This case increases the awareness of a rare malignant subtype of PMT and provides a valuable reference for the diagnosis of this disease.

Type 2 sclerotic Modic change affect fusion result in patients undergoing PLIF with pedicle screw instrumentation: a retrospective study.

BACKGROUND: Bony fusion rate was significantly lower in patients with type 3 Modic change than patients with normal endplates. It is not known whether there are relevant differences in fusion efficiency among patients with type 2 sclerotic Modic change or non-sclerotic Modic change, or no Modic change. METHODS: A retrospective study contained 196 lumbar segments in 123 subjects undergoing posterior lumbar interbody fusion (PLIF) with pedicle screw instrumentation (PSI) to assess the effect of type 2 sclerotic Modic change on fusion efficiency. These endplates were allocated into groups A, B, and C, according to their Modic changes. Group A had endplates with type 2 Modic change and endplate sclerosis. Group B had type 2 Modic change without endplate sclerosis. Group C had neither Modic change nor endplate sclerosis. The presence of Modic change was determined by magnetic resonance imaging (MRI). Endplate sclerosis in type 2 Modic change was detected by computed tomography (CT) before the operation. We collected CT data 3 months to more than 24 months after operation in patients to assess bony fusion. RESULTS: Incidences of bony fusion were 58.8% in group A, 95.0% in group B, 94.3% in group C. The bony fusion rate was significantly lower in group A than in either group B or C. There was no significant difference between groups B and C. Thus, endplates with type 2 sclerotic Modic change had a lower fusion rate in patients undergoing PLIF with PSI. CONCLUSION: Type 2 sclerotic Modic change could be an important factor that affects solid bony fusion in patients undergoing PLIF with PSI. CT may help diagnose endplate sclerosis in patients with type 2 change and inform the choice of the best site for spinal fusion.

Sperm-borne small RNAs improve the developmental competence of pre-implantation cloned embryos in rabbit.

The low efficiency of somatic cell nuclear transfer (SCNT) greatly limits its application. Compared with the fertilized embryo, cloned embryos display abnormal epigenetic modification and other inferior developmental properties. In this study, small RNAs were isolated, and miR-34c and miR-125b were quantified by real-time PCR; results showed that these micro-RNAs were highly expressed in sperm. The test sample was divided into three groups: one was the fertilized group, one was the SCNT control group (NT-C group), and the third group consisted of SCNT embryos injected with sperm-borne small RNA (NT-T group). The level of tri-methylation of lysine 9 on histone H3 (H3K9me3) at the 8-cell stage was determined by immunofluorescence staining, and the cleavage ratio, blastocyst ratio, apoptotic cell index of the blastocyst and total cell number of blastocysts in each group were analyzed. Results showed that the H3K9me3 level was significantly higher in the NT-C group than in the fertilized group and the NT-T group. The apoptosis index of blastocysts in the NT-C group was significantly higher than that in the fertilized group and the NT-T group. The total cell number of SCNT embryos was significantly lower than that of fertilized embryos, and injecting sperm-borne small RNAs could significantly increase the total cell number of SCNT blastocysts. Our study not only demonstrates that sperm-borne small RNAs have an important role in embryo development, but also provides a new strategy for improving the efficiency of SCNT in rabbit.

Biochanin A protect against lipopolysaccharide-induced acute lung injury in mice by regulating TLR4/NF-κB and PPAR-γ pathway.

Acute lung injury (ALI) is a serious respiratory syndrome featured with uncontrolled inflammatory response. Biochanin A has been showed to possess and anti-inflammatory effect. This study intended to explore the suppression of biochanin A on lipopolysaccharide (LPS)-induced ALI in mice. Seven hours later LPS-induced ALI model established, the indexes including, pathological changes, MPO activity, wet/dry ratio, proinflammatory cytokines TNF-α, IL-1ß, and IL-6, production, as well as and TLR4/NF-κB and PPAR-γ signaling pathway expression were compared bwtween different groups. In addition, bronchoalveolar lavage fluid (BALF) was collected and the levels of total protein, inflammatory cells and TNF-α, IL-1ß, and IL-6 were detected. The results revealed that LPS lead to significantly lung pathological injury, and damage of lung vascular permeability showing by higher lung wet/dry ratio and total protein levels in the BALF when compared to the control group mice. However, these changes significantly reversed by biochanin A. Moreover, the levels of inflammatory cells in BALF, proinflammatory cytokines TNF-α, IL-1ß, and IL-6, in both lung and BALF were also dose-dependently reduced by biochanin A during ALI process. To investigate the anti-inflammatory mechanisms of biochanin A, we found that biochanin A significantly inhibited the activation of TLR4/NF-κB signaling pathway induced by LPS. Furthermore, the expression of PPAR-γ also markedly increased in the mice after treated with biochanin A. In conclusion, biochanin A alleviated LPS-induced ALI by inhibiting the inflammatory response, which was mediated via down-regulating the activation of TLR4/NF-κB signaling pathway and enhancing the expression of PPAR-γ.

Odontoid incidence: a constant cervical anatomical feature evident in standing plain radiographs and supine magnetic resonance images.

OBJECTIVE: To assess whether there is a difference between measurements of odontoid incidence (OI) and other cervical sagittal parameters by X-ray radiography and those by supine magnetic resonance imaging (MRI). METHODS: Standing X-ray and supine MRI images of 42 healthy subjects were retrospectively analyzed. Surgimap software was employed to measure cervical sagittal parameters including OI, odontoid tilt (OT), C2 slope (C2S), C0-2 angle, C2-7 angle, T1 slope (T1S) and T1S-cervical lordosis (CL). Paired samples t-test was applied to determine the difference between parameters measured by standing X-ray and those by supine MRI. In addition, the statistical correlation between the parameters were compared. The prediction of CL was performed and validated using the formula CL = 0.36 × OI - 0.67 × OT - 0.69 × T1S. RESULTS: Significant correlations and differences were found between cervical sagittal parameters determined by X-ray and those by MRI. OI was verified to be a constant anatomic parameter and the formula CL = 0.36 × OI - 0.67 × OT - 0.69 × T1S can be used to predict CL in cervical sagittal parameters. CONCLUSIONS: OI is verified as a constant anatomic parameter, demonstrating the necessity of a combined assessment of cervical sagittal balance by using standing X-ray and supine MRI. The formula CL = 0.36 × OI - 0.67 × OT - 0.69 × T1S can be applied to predict CL in cervical sagittal parameters.

A novel extraction method for three ochratoxins in human urine based on polystyrene/polyethersulfone electrospun nanofibers coated with copper nanoparticles.

In this study, four types of nanofibers were prepared via electrospinning and characterized through SEM, TEM, EDS, FTIR, TG, XPS and water contact angle analyses, and the novel polystyrene/polyethersulfone nanofibers coated with copper nanoparticles (PS/PES-CuNPs nanofibers) were developed as an ideal adsorbent for the extraction of three ochratoxins from human urine. The solid-phase extractant of sample pretreatment displayed preferable sensitivity and an extraction effect, and the analytical method based on the novel packed-fiber solid-phase extraction strategy followed by high performance liquid chromatography-fluorescence detection (PFSPE-HPLC-FLD) achieved an exceedingly low limit of detection (LOD) and limit of quantification (LOQ) of 0.108-0.162 µg L-1 and 0.658-0.701 µg L-1, respectively; a high spiked recovery of 71.3-92.0% and a lower adsorption time of 7 min, thus demonstrating excellent results compared with other reported adsorbents for ochratoxins from various samples. With the application of this method for the detection of ochratoxins in human urine samples, six in thirty samples were tested positive. This study confirmed that the PS/PES-CuNP nanofibers and PFSPE showed promising potential as a sensitive method for simultaneous extraction and detection of ochratoxins in complex samples.