Insights into the discovery and intervention of metalloproteinase in marine hazardous jellyfish.

The proliferation of toxic organisms caused by changes in the marine environment, coupled with the rising human activities along the coastal lines, has resulted in an increasing number of stinging incidents, posing a serious threat to public health. Here, we evaluated the systemic toxicity of the venom in jellyfish Chrysaora quinquecirrha at both cellular and animal levels, and found that jellyfish tentacle extract (TE) has strong lethality accompanied by abnormal elevation of blood biochemical indicators and pathological changes. Joint analysis of transcriptome and proteome indicated that metalloproteinases are the predominant toxins in jellyfish. Specially, two key metalloproteinases DN6695_c0_g3 and DN8184_c0_g7 were identified by mass spectrometry of the red blood cell membrane and tetracycline hydrochloride (Tch) inhibition models. Structurally, molecular docking and kinetic analysis are employed and observed that Tch could inhibit the enzyme activity by binding to the hydrophobic pocket of the catalytic center. In this study, we demonstrated that Tch impedes the metalloproteinase activity thereby reducing the lethal effect of jellyfish, which suggests a potential strategy for combating the health threat of marine toxic jellyfish.

Competition-Induced Macroscopic Superlubricity of Ionic Liquid Analogues by Hydroxyl Ligands Revealed by in Situ Raman.

High load-bearing capacity is one of the crucial indicators for liquid superlubricants to move toward practicality. However, some of the current emerging systems not only have low contact pressures but also are highly susceptible to further degradation due to water adsorption and even superlubricity failure. Herein, a novel choline chloride-based ionic liquid analogues (ILAs) of a superlubricant with triethanolamine (TEOA) as the H-bond donor is reported for the first time; it obtains an ultralow coefficient of friction (0.005) and high load-bearing capacity (360 MPa, more than 2 times that of similar systems) due to adsorption of a small amount of water (<5 wt %) from the air. In situ Raman combined with 1H NMR and FTIR techniques reveals that adsorbed water competes with the hydroxyl group of TEOA for coordination with Cl-, leading to the conversion of some strong H-bonds to weak H-bonds in ILAs; the localized strong H-bonds and weak H-bonds endow the ILAs with high load-bearing capacity and the formation of ultralow shear-resistance sliding interfaces, respectively, under the shear motion. This study proposes a strategy to modulate the interactions between liquid species using adsorbed water from air as a competing ligand, which provides new insights into the design of ILA-based macroscopic liquid superlubricants with a high load-bearing capacity.

[Immune Reconstitution after BTKi Treatment in Chronic Lymphocytic Leukemia].

OBJECTIVE: To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia (CLL). METHODS: The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively. RESULTS: The median age of 59 CLL patients was 60.5(36-78). After one year of BTKi treatment, the CLL clones (CD5 +/CD19 +) of 51 cases (86.4%) were significantly reduced, in which the number of cloned-B cells decreased significantly from (46±6.1)×109/L to (2.3±0.4)×109/L (P =0.0013). But there was no significant change in the number of non-cloned B cells (CD19 + minus CD5 +/CD19 +). After BTKi treatment, IgA increased significantly from (0.75±0.09)g/L to (1.31±0.1)g/L (P <0.001), while IgG and IgM decreased from (8.1±0.2)g/L and (0.52±0.6)g/L to (7.1±0.1)g/L and (0.47±0.1)g/L, respectively (P <0.001, P =0.002). BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients, which manifested as both a decrease in total number of T cells from (2.1±0.1)×109/L to (1.6±0.4)×109/L and NK/T cells from (0.11±0.1)×109/L to (0.07±0.01)×109/L (P =0.042, P =0.038), both an increase in number of CD4 + cells from (0.15±6.1)×109/L to (0.19±0.4)×109/L and CD8 + cells from (0.27±0.01)×109/L to (0.41±0.08)×109/L (both P <0.001). BTKi treatment also up-regulated the expression of interleukin (IL)-2 while down-regulated IL-4 and interferon (IFN)-γ. However, the expression of IL-6, IL-10, and tumor necrosis factor (TNF)-α did not change significantly. BTKi treatment could also restored the diversity of TCR and BCR in CLL patients, especially obviously in those patients with complete remission (CR) than those with partial remission (PR). Before and after BTKi treatment, Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001 (P <0.001), while in patients with PR was 0.01±0.03 and 0.05±0.02 (P >0.05), respectively. Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15 (P <0.001), while in patients with PR was 0.15±0.009 and 0.23±0.18 (P <0.05), respectively. CONCLUSIONS: BTKi treatment can shrink the clone size in CLL patients, promote the expression of IgA, increase the number of functional T cells, and regulate the secretion of cytokines such as IL-2, IL-4, and IFN-γ. BTKi also promote the recovery of diversity of TCR and BCR. BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Highly Concentrated Electrolyte Superlubricants Enhanced by Interfacial Water Competition Around Chemically Active MgO Additives.

The low concentration of water-based lubricants and the high chemical inertness of the additives involved are often regarded as basic norms in the design of liquid lubricants. Herein, a novel liquid superlubricant of an aqueous solution containing a relatively high concentration of salt, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), is reported for the first time, and the superlubricity stability and load-bearing capacity of the optimized system (MgO0.10/LiTFSI10) are effectively strengthened by the addition of only trace (0.10 wt %) water-chemically active MgO additives. It demonstrates higher applicable loads, lower COF (∼0.004), and stability relative to the base solution. Only a trace amount of MgO additive is needed for the superlubricity, which makes up for the cost and environmental deficiencies of LiTFSI10. The weak interaction region between free water and the outer-layer water of Li+ hydration shells becomes a possible ultralow shear resistance sliding interface; the Mg(OH)2 layer, generated by the reaction of MgO with water, further creates additional weakly interacting interfaces, leading to the formation of an asymmetric contact between the clusters/particles within the hydrodynamic film by moderating the competition between interfacial water and free water, thus achieving high load-bearing macroscopic superlubricity. This study deepens the contribution of electrolyte concentration to ionic hydration and superlubricity due to the low shear slip layer formed by interfacial water competition with water-activated solid additives, providing new insights into the next generation of high load-bearing water-based liquid superlubricity systems.

Synthesis and photodynamic activity of novel thieno[3,2-b]thiophene fused BODIPYs with good bio-solubility and anti-aggregation effect.

To discover new photosensitizers with long wavelength UV-visible absorption, high efficiency, and low side effects for photodynamic therapy, here, a series of novel thieno[3,2-b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. These compounds had a distinct absorption band at 640-680 nm, fluorescence emission at 650-760 nm, and good solubility with anti-aggregation effects. These new compounds possessed obvious singlet oxygen generation ability and photodynamic anti-Eca-109 cancer cells activities in vitro. Among them, compound II4 could be well uptaked by Eca-109 cells, and result in the apoptosis after laser irradiation, and have outstanding photodynamic efficiency both in vitro and in vivo. Therefore, II4 could be considered as a potential photosensitizer drug candidate for PDT and photo-imaging.

Comparison of Outcomes of Facial Reanimation Between the Use of Cross-facial Nerve Graft and the Masseteric Nerve as the Donor Nerve for Reinnervation of Gracilis Muscle Flap Transfer.

BACKGROUND: In patients with facial paralysis, the free functional gracilis muscle transfer is preferred for facial reanimation. The choice of an adequate motor nerve to innervate the transplanted gracilis muscle is one of the procedure's key components. We present a comparative study between cross-facial nerve graft (CFNG) and masseteric nerve as donor nerves for reinnervated gracilis flap transfer in patients with complete facial paralysis. MATERLALS AND METHODS: Retrospective analysis was performed on all patients with complete facial paralysis who had a free functional gracilis muscle transfer for facial reanimation between January 2014 and December 2021. Only those who received gracilis transfer reinnervated by either CFNG or masseteric nerve were included in this study. The smile excursion and lip angle were measured for evaluating the outcomes postoperatively. RESULTS: The inclusion criteria were met by a total of 21 free functional gracilis muscle transfers, of which 11 were innervated by CFNG and 10 by the masseteric nerve. Both surgical procedures resulted in a highly considerable smile excursion of the reanimated side and postoperative improvement of static or dynamic lip angle. Masseteric nerve coaptation led to greater smile excursion and more significant improvement of dynamic lip angle than CFNG. CONCLUSIONS: For patients who have complete facial paralysis, face reanimation can be successfully accomplished by free gracilis transfer reinnervated by the CFNG or the masseteric nerve. In particular, the masseteric nerve is a reliable choice for dynamic smile reanimation.

Exosomes from adipose-derived stem cells alleviate premature ovarian failure via blockage of autophagy and AMPK/mTOR pathway.

Objective: The objective of this study was to investigate the effects and mechanisms of adipose-derived stem cell-derived exosome (ADSCs-Exo) in treating premature ovarian failure (POF). Methods: We constructed a POF mouse model through intraperitoneal injection of cyclophosphamide, followed by the administration of the autophagy inhibitor 3-methyladenine (3-MA). Pathological injury, follicle stimulating hormone (FSH), malondialdehyde (MDA), reactive oxygen species (ROS), estradiol (E2), superoxide dismutase (SOD), granulosa cell (GC) apoptosis, and autophagy were assessed. Exosomes isolated from ADSCs were used to treat POF in mice. The AMPK-mTOR pathway and its proteins (p-AMPK and p-mTOR) were evaluated. A POF cell model was established using cyclophosphamide-treated human ovarian granulosa-like tumor (KGN) cells. We administered ADSCs-Exo and rapamycin to validate the mechanism of ADSCs-Exo against POF. Results: In POF mice, 3-MA treatment attenuated pathological injuries, decreased FSH, MDA, and ROS levels, and increased E2 and SOD levels. 3-MA treatment also inhibited GC apoptosis and autophagy. ADSCs-Exo alleviated pathological injuries, improved ovarian morphology and function, and reduced oxidative stress in POF mice. ADSCs-Exo inhibited GC apoptosis and autophagy. ADSCs-Exo downregulated the expression of AMPK/mTOR pathway proteins (p-AMPK and p-mTOR). In the POF cell model, ADSCs-Exo and rapamycin inhibited AMPK/mTOR-mediated autophagy. Conclusion: ADSCs-Exo inhibits POF through the inhibition of autophagy and the AMPK/mTOR pathway. This study provides a potential target for the clinical treatment of POF.

Psychometric properties of the Chinese version of the Trait Gratitude to Nature Scale.

Objective: The purpose of this study was to evaluate the reliability and validity of the Chinese version of the Trait Gratitude to Nature Scale (TGNS) for Chinese college students. Methods: The original English version of the TGNS was translated into Chinese. Subsequently, two samples consisting of 1,131 Chinese university students from Inner Mongolia Autonomous Region was recruited through online surveys to evaluate the psychometric properties of the Chinese version of the TGNS, including the discrimination, construct validity, criterion validity, reliability and gender invariance. Results: The Chinese version of the TGNS showed good psychometric properties. The item-total correlation coefficients of the scale ranged from 0.813 to 0.909. Exploratory factor analysis using data from Sample 1 (n = 617) demonstrated that the Chinese version of the TGNS has one factor. The confirmatory factor analysis using data from Sample 2 (n = 514) showed that the Chinese version of the TGNS has appropriate construct validity (χ2/df = 4.157, RMSEA = 0.078, TLI = 0.943 and CFI = 0.967). The significant correlation between the Chinese version of the TGNS and all the other criterion scale scores (p < 0.001) indicated that the Chinese version of the TGNS displays good criterion validity. The test-retest reliability was 0.914, using the sub-sample of Sample 2 (n = 127). The results of gender invariance test indicated that the Chinese version of the TGNS has entire equivalence between the two genders. Conclusion: The Chinese version of the TGNS has satisfactory psychometric properties in the Chinese cultural context and can be used as s a reliable and valid instrument to assess trait gratitude to nature.

Berberine ameliorates the neurological dysfunction of the gastric fundus by promoting calcium channels dependent release of ACh in STZ-induced diabetic rats.

Background: It has been reported diabetic gastroparesis is related to diabetic autonomic neuropathy of the gastrointestinal tract, and berberine (BBR) could ameliorate diabetic central and peripheral neuropathy. However, the influence of BBR on the function and motility of the gastric fundus nerve is unclear. Methods: A diabetic rat model was constructed, and HE staining was used to observe the morphological changes in the gastric fundus. The changes in cholinergic and nitrogen-related neurochemical indexes and the effects of BBR on them were measured using Elisa. The effects of BBR on the neural function and motility of gastric fundus were investigated by electric field stimulation (EFS) induced neurogenic response in vitro. Results: In the early stage of STZ-induced diabetic rats, the contractile response of gastric fundus induced by EFS was disorder, disturbance of contraction amplitude, and the cell bodies of neurons in the myenteric plexus of gastric fundus presented vacuolar lesions. Administration with BBR could improve the above symptoms. BBR further enhanced the contraction response in the presence of a NOS inhibitor or the case of inhibitory neurotransmitters removal. Interestingly, the activity of ACh could affect NO release directly and the enhancement of BBR on contractile response was canceled by calcium channel blockers completely. Conclusions: In the early stage of STZ-induced diabetic rats, the neurogenic contractile response disorder of the gastric fundus is mainly related to cholinergic and nitrergic nerve dysfunction. BBR promotes the release of ACh mainly by affecting the calcium channel to improve the neurological dysfunction of the gastric fundus.

Functional and aesthetic outcomes of abdominal full-thickness skin grafts in paediatric postburn digital and palmar flexion contractures.

The study aimed to assess the functional and aesthetic outcomes of abdominal full-thickness skin grafts (FTSGs) in paediatric postburn digital and palmar flexion contractures. The digital and palmar functions and aesthetics of 50 children who met the criteria were evaluated at pre-operation, the 3rd- and 12th-month post-operation, respectively. In the evaluation, the Vancouver Scar Scale (VSS), total active movement (TAM), and Jebsen-Taylor Hand Function Test (JHFT) were used. The contralateral, unaffected hand served as the criteria for functional recovery. The complications of donor sites were observed, and the take rate of skin grafts was calculated. The VSS scores at the 3rd and 12th months post-operation were lower than those before the operation. The TAM of each finger was improved at the 3rd and 12th months post-operation, compared with that before the operation. There was a significant difference in the time to complete the JHFT between the affected hand and the unaffected at the 3rd month post-operation, but no significant difference between them at the 12th month post-operation. The excellent and good take rate of the skin grafts was 90.00%.No donor site complications were observed. The abdominal FTSGs are effective in repairing paediatric digital and palmar scar contractures, with satisfying functional and aesthetic results, especially in large defects after scar release and resection.

In Situ Raman Study of Voltage Tolerance Up to 2.2 V of Ionic Liquid Analogue Supercapacitor Electrolytes Immune to Water Adsorption Conferred by Amphoteric Imidazole Additives.

Ionic liquid analogues (ILAs) are promising electrolytes for supercapacitors due to their low cost and considerable voltage (>2.0 V). However, the voltage is <1.1 V for water-adsorbed ILAs. Herein for the first time, an amphoteric imidazole (IMZ) additive is reported to address this concern by reconfiguring the solvent shell of ILAs. Addition of only 2 wt % IMZ increases the voltage from 1.1 to 2.2 V, with an increase in capacitance from 178 to 211 F g-1 and an increase in energy density from 6.8 to 32.6 Wh kg-1. In situ Raman reveals that the strong H-bonds formed by IMZ with completive ligands 1,3-propanediol and water induce a reversal of the polarity of the solvent shells, suppressing absorbed water electrochemical activity and thus increasing the voltage. This study solves the problem of low voltage for water-adsorbed ILAs and reduces the equipment cost of ILA-based supercapacitor assembly (e.g., assembly in air without a glovebox).

Subcutaneous stretching enlarges adjacent vertebral artery instantly in patients with cervicogenic dizziness: Two case reports.

RATIONALE: Fu's subcutaneous needling (FSN) is effective for cervicogenic dizziness (CGD), which is often a result of vascular problems. Here, we attribute the positive treatment effect of FSN for CGD to improvements in vascular problems. PATIENT CONCERN: Two patients were experiencing low quality of life due to reproducible dizziness. DIAGNOSIS: Two patients with cervical spine disorder, presented with neck pain and reproducible dizziness. Other causes of dizziness were excluded. INTERVENTIONS: Case 1 received 1 session of FSN treatment, while case 2 received 3 sessions of FSN treatment in a month. OUTCOMES: The dizziness and neck pain experienced by both patients instantly improved significantly after FSN treatment, and the luminal diameter of the vertebral artery (VA) measured by carotid and VA ultrasound enlarged simultaneously up to 1.29-fold and 1.09-fold for both cases. According to the Hagen-Poiseuille equation, the blood flow volume increased 2.77-fold and 1.43-fold, respectively. Case 2 recovered from CGD with 1.19-fold VA luminal diameter increment and about 2.01-fold increase of blood flow volume in a month. LESSONS: Subcutaneous stretching provides a safe, convenient and immediate solution to CGD, and supports the diagnosis and treatment of CGD under carotid and VA ultrasound. This study suggests that stretching subcutaneously can influence adjacent VA, which may also help improve some cerebrovascular diseases.

Unravelling High-Load Superlubricity of Ionic Liquid Analogues by In Situ Raman: Incomplete Hydration Induced by Competitive Exchange of External Water with Crystalline Water.

A high load-carrying capacity is the key to the practicality of liquid superlubricity, but it is difficult to achieve high load and low friction simultaneously by relying solely on a liquid film. Herein, a choline chloride-based ionic liquid analogue (ILA) macroscale superlubricant is first reported by tuning down strong hydrogen bonding in the ILA via introducing 2-10 wt % water, with a high load of 160 MPa and a low coefficient of friction of 0.006-0.008. In situ Raman reveals that competitive exchange between external water and crystalline water induces weak H-bond-dominated incomplete hydration, conferring a low-shear interface and considerable load-carrying capacity inside the lubricant. It is a hydrodynamic lubrication film rather than a tribochemical/physical adsorption film, allowing it to be applied to friction pairs of various materials. This study unveils the principle of water mediation of high-viscosity ILAs and also provides new insights into the design of practical ILA-based superlubrication materials with high load-carrying capacity.

Modulators of ASIC1a and its potential as a therapeutic target for age-related diseases.

Age-related diseases have become more common with the advancing age of the worldwide population. Such diseases involve multiple organs, with tissue degeneration and cellular apoptosis. To date, there is a general lack of effective drugs for treatment of most age-related diseases and there is therefore an urgent need to identify novel drug targets for improved treatment. Acid-sensing ion channel 1a (ASIC1a) is a degenerin/epithelial sodium channel family member, which is activated in an acidic environment to regulate pathophysiological processes such as acidosis, inflammation, hypoxia, and ischemia. A large body of evidence suggests that ASIC1a plays an important role in the development of age-related diseases (e.g., stroke, rheumatoid arthritis, Huntington's disease, and Parkinson's disease.). Herein we present: 1) a review of ASIC1a channel properties, distribution, and physiological function; 2) a summary of the pharmacological properties of ASIC1a; 3) and a consideration of ASIC1a as a potential therapeutic target for treatment of age-related disease.

Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.

Rheumatoid arthritis is a common autoimmune disease that results from the deposition of antibodies-autoantigens in the joints, leading to long-lasting inflammation. The main features of RA include cartilage damage, synovial invasion and flare-ups of intra-articular inflammation, and these pathological processes significantly reduce patients' quality of life. To date, there is still no drug target that can act in rheumatoid arthritis. Therefore, the search for novel drug targets has become urgent. Due to their unique physicochemical properties, calcium ions play an important role in all cellular activities and the body has evolved a rigorous calcium signaling system. Calcium-permeable channels, as the main operators of calcium signaling, are widely distributed in cell membranes, endoplasmic reticulum membranes and mitochondrial membranes, and mediate the efflux and entry of Ca2+. Over the last century, more and more calcium-permeable channels have been identified in human cells, and the role of this large family of calcium-permeable channels in rheumatoid arthritis has gradually become clear. In this review, we briefly introduce the major calcium-permeable channels involved in the pathogenesis of RA (e.g., acid-sensitive ion channel (ASIC), transient receptor potential (TRP) channel and P2X receptor) and explain the specific roles and mechanisms of these calcium-permeable channels in the pathogenesis of RA, providing more comprehensive ideas and targets for the treatment of RA.

Carbon/Basalt Fibers Hybrid Composites: Hybrid Design and the Application in Automobile Engine Hood.

The low-velocity impact properties and the optimal hybrid ratio range for improving the property of hybrid composites are studied, and the application of hybrid composites in automobile engine hoods is discussed in this paper. The low-velocity impact properties of the hybrid composite material are simulated under different stacking sequences and hybrid ratios by finite element simulation, and the accuracy of the finite element model (FEM) is verified through experiments. Increasing the proportion of carbon fiber (CF) in the hybrid layer and placing the basalt fiber (BF) on the compression side can improve the energy absorption capacity under low-velocity impact loads. CF/BF hybrid composite hoods are optimized based on the steel hood and the low-velocity impact performance of the hybrid composite. The BCCC layer absorbs the most energy under low-velocity impact loads. Compared with CFRP, the energy absorbed under 10 J and 20 J impact energy is increased by 26.1% and 14.2%, respectively. Through the low-velocity impact properties of hybrid composites, we found that placing BF on the side of the load and keep the ratio below 50%, while increasing the proportion of CF in the hybrid laminate can significantly improve the property of the hybrid laminate. The results show that the stiffness and modal properties of the hybrid composite can meet the design index requirements, and the pedestrian protection capability of the hood will also increase with the increase in the proportion of BF.

SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19.

Over the past two years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections, resulting in an unprecedented pandemic of coronavirus disease 2019 (COVID-19). As the virus spreads through the population, ongoing mutations and adaptations are being discovered. There is now substantial clinical evidence that demonstrates the SARS-CoV-2 variants have stronger transmissibility and higher virulence compared to the wild-type strain of SARS-CoV-2. Hence, development of vaccines against SARS-CoV-2 variants to boost individual immunity has become essential. However, current treatment options are limited for COVID-19 caused by the SARS-CoV-2 variants. In this review, we describe current distribution, variation, biology, and clinical features of COVID-19 caused by SARS-CoV-2 variants (including Alpha (B.1.1.7 Lineage) variant, Beta (B.1.351 Lineage) variant, Gamma (P.1 Lineage) variant, Delta (B.1.617.2 Lineage) variant, and Omicron (B.1.1.529 Lineage) variant and others. In addition, we review currently employed vaccines in clinical or preclinical phases as well as potential targeted therapies in an attempt to provide better preventive and treatment strategies for COVID-19 caused by different SARS-CoV-2 variants.

Ferroelectric benzimidazole additive-induced interfacial water confinement for stable 2.2 V supercapacitor electrolytes exposed to air.

Deep eutectic solvents (DESs) are known as low-cost and environmentally friendly electrolytes for supercapacitors. However, because DESs are particularly vulnerable to moisture adsorption in the air, the voltage window (<1.2 V) is significantly lower than expected. Herein, we report a new ferroelectric benzimidazole (BI) additive that, by restricting water electrochemical activity at the DES/carbon electrode interface, allows air-exposed DESs to reach a high voltage of 2.2 V. The optimized DES with 0.5 wt% BI addition not only increases the voltage but also the capacitance and energy density while maintaining excellent cycling stability. This study addresses the voltage drop of DESs in air, providing insights into the design of additives that inhibit interfacial water splitting.