Immune Responses and Protection Profiles in Mice Induced by Subunit Vaccine Candidates Based on the Extracellular Domain Antigen of Respiratory Syncytial Virus G Protein Combined with Different Adjuvants.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease of infants and older people. There is an urgent need for safe and effective vaccines against RSV infection. In this study, we analyzed the effects of the immune response and protection with the RSV recombinant G protein extracellular domain (Gecto) combined with various adjuvants as novel subunit vaccines in mice. All groups receiving RSV Gecto combined with adjuvants exhibited robust humoral and cellular immunity compared to those receiving an adjuvant alone or inactivated RSV vaccine. The greatest effect was observed in mice receiving Gecto combined with a CpG ODN + Alum salt adjuvant, resulting in the highest production of neutralizing antibodies against both RSV A and B subtypes, G-specific IgG and IFN-γ production in splenocytes, and interleukin-2 and interferon-γ expression in CD4+ T cells. Significant humoral and cellular immune responses were observed in mice immunized with Gecto combined with AddaS03™ or cyclosporin A adjuvants. The vaccine containing the AddaS03™ adjuvant showed significantly high expression of interleukin-4 in CD4+ T cells. Cross-protection against a challenge with either RSV A or B subtypes was observed in the Gecto plus adjuvant groups, resulting in a significant decrease in viral load and reduced pathological damage in the mouse lungs. These findings offer valuable insights into the development and application of recombinant RSV G-subunit vaccines with adjuvants.

Risk factors affecting long-term efficacy of ultrasound-guided high-intensity focused ultrasound treatment for multiple uterine fibroids.

OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.

[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

Distinguish MnO2/Mn2+ Conversion/ Zn2+ Intercalation/ H+ Conversion Chemistries at Different Potentials in Aqueous Zn||MnO2 Batteries.

The rechargeable aqueous Zn||MnO2 chemistry has been extensively explored, but its electrochemical reaction mechanisms, especially in the context of MnO2/Mn2+ conversion and Zn2+/H+ intercalation chemistry, remain not fully understood. Here, we designed an amphiphilic hydrogel electrolyte, which distinguished the MnO2/Mn2+ conversion, Zn2+ intercalation, and H+ intercalation and conversion processes at three distinct discharge plateaus of an aqueous Zn||MnO2 battery. The amphiphilic hydrogel electrolyte is featured with an extended electrochemical stability window up to 3.0 V, high ionic conductivity, Zn2+-selective ion tunnels, and hydrophobic associations with cathode materials. This specifically designed electrolyte allows the MnO2/Mn2+ conversion reaction at a discharge plateau of 1.75 V. More interesting, the discharge plateaus of ~1.33 V, previously assigned as the co-intercalation of Zn2+ and H+ ions in the MnO2 cathode, are specified as the exclusive intercalation of Zn2+ ions, leading to an ultra-flat voltage plateau. Furthermore, with a distinct three-step electrochemical energy storage process, a high areal capacity of 1.8 mAh cm-2 and high specific energy of 0.858 Wh cm-2, even at a low MnO2 loading mass of 0.5 mg cm-2 are achieved. To our knowledge, this is the first report to fully distinguish different mechanisms at different potentials in aqueous Zn||MnO2 batteries.

[Effects of Pesticides Use on Pesticides Residues and Its Environmental Risk Assessment in Xingkai Lake（China）].

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L-1. Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L-1. In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

The role of amino acid metabolism in autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an inflammatory chronic liver disease with persistent and recurrent immune-mediated liver injury. The exact cause of AIH is still not fully understood, but it is believed to be primarily due to an abnormal activation of the immune system, leading to autoimmune injury caused by the breakdown of autoimmune tolerance. Although the pathogenesis of AIH remains unclear, recent studies have shown that abnormalities in amino acid metabolism play significant roles in its development. These abnormalities in amino acid metabolism can lead to remodeling of metabolic processes, activation of signaling pathways, and immune responses, which may present new opportunities for clinical intervention in AIH. In this paper, we first briefly outline the recent progress of clinically relevant research on AIH, focusing on the role of specific amino acid metabolism (including glutamine, cysteine, tryptophan, branched-chain amino acids, etc.) and their associated metabolites, as well as related pathways, in the development of AIH. Furthermore, we discuss the scientific issues that remain to be resolved regarding amino acid metabolism, AIH development and related clinical interventions, with the aim of contributing to the future development of amino acid metabolism-based as a new target for the clinical diagnosis and treatment of AIH.

A retrospective analysis of heavy metals and multi elements in the Yangtze River Basin: Distribution characteristics, migration tendencies and ecological risk assessment.

The Yangtze River is the third longest river in the world with more than 6300 km, covering 0.4 billion people. However, the aquatic ecosystem of the Yangtze River has been seriously damaged in the past decades due to a rapid development of economic and industrialization along the coast. In this study, we first established a dataset of fifty elements, including nine common heavy metals (HMs) and forty-one other elements, in the Yangtze River Basin through the collection of historical data from 2000 to 2020, and then analyzed their spatiotemporal distribution characteristics. The results indicated that the Three Gorges Reservoir (TGR), a region formed by the construction of the Three Gorges Dam (TGD), may act as a sink for these elements from upstream regions. The concentrations of seven elements in surface water and 13 elements in sediment obviously increased from the upstream region of the TGR to the TGR. In addition, ten elements in the surface water and 5 elements in the sediments clearly decreased, possibly because of the interception effects of the TGD. On a timescale, Cr obviously tended to migrate from the water phase to the sediment; Pb tended to migrate from the sediment to the water phase. In the ecological risk assessment, all common HMs in surface water were supposed to have negligible risks as protecting 90 % of aquatic organisms; Cd (210.2), Hg (58.0) and As (43.1) in sediment posed high and moderate ecological risks using the methodology of the potential ecological risk index. Furthermore, Hunan Province is at considerable risk according to the sum of the potential risk index (314.8) due to Cd pollution (66.8 %). These fundamental data and results will support follow-up control strategies for elements and policies related to aquatic ecosystem protection in the Yangtze River Basin.

Distribution Characteristics and Risk Assessment of 57 Pesticides in Farmland Soil and the Surrounding Water.

To investigate the effect of pesticide use on surface water, the concentration and distribution characteristics of 57 pesticides and 3 degradation products were analyzed in the farmland soil and surface water in the Xingkai Lake area, including water from paddy fields, drainages and the Xingkai Lake, in Heilongjiang Province, China. Forty-three pesticides and three degradation products were detected in farmland soil. In dry field (corn and soybean field) soil, the main detected pesticides were atrazine and acetochlor with mean concentrations of 26.09 ng·g-1 and 49.08 ng·g-1, respectively. In paddy field soil, oxadiazon, mefenacet and chlorpyrifos were the main detected pesticides with mean concentrations of 14.32 ng·g-1, 78.60 ng·g-1 and 20.03 ng·g-1, respectively. In the surrounding water, including water from paddy fields, drainages and Xingkai Lake, the total concentrations of contaminants detected in the water samples ranged from 71.19 ng·L-1 to 10,145.76 ng·L-1. Of the three sampling periods, the mean concentration of contaminants in the water exhibited its peak during the vegetative period. In the analysis of the drainage water, the primary pesticides detected were atrazine, acetochlor and buprofezin with mean concentrations of 354.83 ng·L-1, 109.09 ng·L-1 and 254.56 ng·L-1, respectively. Atrazine, simetryn, buprofezin and isoprothiolane were the main pesticides detected in Xingkai Lake water, with the mean concentrations of 222.35 ng·L-1, 112.76 ng·L-1, 301.87 ng·L-1 and 138.02 ng·L-1, respectively. The concentrations of contaminants could be correlated with drainage, Da Xingkai Lake and Xiao Xingkai Lake water (ρ > 0.8) suggested that the source of these contaminants in drainage and Xingkai Lake water could be the same. The maximum potentially affected fraction (PAF) values of atrazine, chlorpyrifos and prometryn were higher than 5% in Xingkai Lake water, resulting in high ecological risks.

Fine Tuning Water States in Hydrogels for High Voltage Aqueous Batteries.

Hydrogels are widely used as quasi-solid-state electrolytes in aqueous batteries. However, they are not applicable in high-voltage batteries because the hydrogen evolution reaction cannot be effectively suppressed even when water is incorporated into the polymer network. Herein, by profoundly investigating the states of water molecules in hydrogels, we designed supramolecular hydrogel electrolytes featuring much more nonfreezable bound water and much less free water than that found in conventional hydrogels. Specifically, two strategies are developed to achieve this goal. One strategy is adopting monomers with a variety of hydrophilic groups to enhance the hydrophilicity of polymer chains. The other strategy is incorporating zwitterionic polymers or polymers with counterions as superhydrophilic units. In particular, the nonfreezable bound water content increased from 0.129 in the conventional hydrogel to >0.4 mg mg-1 in the fabricated hydrogels, while the free water content decreased from 1.232 to ∼0.15 mg mg-1. As a result, a wide electrochemical stability window of up to 3.25 V was obtained with the fabricated hydrogels with low concentrations of incorporated salts and enhanced hydrophilic groups or superhydrophilic groups. The ionic conductivities achieved with our developed hydrogel electrolytes were much higher than those in the conventional highly concentrated salt electrolytes, and their cost is also much lower. The designed supramolecular hydrogel electrolytes endowed an aqueous K-ion battery (AKIB) system with a high voltage plateau of 1.9 V and contributed to steady cycling of the AKIB for over 3000 cycles. The developed supramolecular hydrogel electrolytes are also applicable to other batteries, such as aqueous lithium-ion batteries, hybrid sodium-ion batteries, and multivalent-ion aqueous batteries, and can achieve high voltage output.

Depth-dependent variations of physicochemical properties of sedimentary dissolved organic matter and the influence on the elimination of typical pharmaceuticals.

Sedimentary dissolved organic matter (DOM) could exert a significant influence on the transformation of trace organic contaminants. However, the variations of sedimentary DOM properties with depth and their impact on trace organic contaminants biodegradation remain unclear. In this study, the qualitative changes in DOM properties with depth were assessed using spectral techniques. Specifically, within the sediment range of 0-30 cm, humic acid and fulvic acid fractions exhibited higher degrees of humification and aromatization at 10-20 cm, while hydrophilic fractions showed higher degrees of humification and aromatization at 20-30 cm. Furthermore, electrochemical methods were employed to quantitatively assess the electron transfer capacity of sedimentary DOM at different depths, which displayed consistent variation trend with humification and aromatization degree. The high degree of humification and aromatization, along with strong electron-accepting capability of DOM, significantly enhanced the biodegradation rates of tetracycline and ritonavir. To gain deeper insights into the influence of molecular composition of DOM on its properties, two-dimensional gas chromatography-quadrupole mass spectrometry analysis revealed that quinones and phenolic hydroxyl compounds govern the redox reactivity of DOM. Simulated experiment of DOM-mediated biodegradation of typical pharmaceuticals confirmed the role of quinones and phenolic hydroxyl groups in the redox reactivity of DOM.

Crystal Orientation Engineering of Perfectly Matched Heterogeneous Textured ZnSe for an Enhanced Interfacial Kinetic Zn Anode.

Uncontrollable dendrite formation in the Zn anode is the bottleneck of the commercialization of rechargeable aqueous zinc-based batteries (RAZBs). Interface, the location of the charge transfer process occuring, can significantly affect the further morphology evolution in ways that have not yet been fully comprehended, for example, the crystal facet and orientation of the coating layer. In this study, we demonstrated that the morphology and kinetics of the Zn anode could be tuned by the crystal facet. The fabricated textured ZnSe (T-ZnSe) layer can significantly enhance the reaction kinetics and induce uniform (0002)Zn deposition. In stark contrast, the polycrystalline P-ZnSe coating hinders the charge transfer process at the interface. With this T-ZnSe@Zn as the anode, the full cell with an I2 cathode and a practical areal capacity (2 mAh cm-2) can work well for 900 cycles. The effectiveness of this anode has also been testified by a pouch cell with an overall capacity of 150 mAh. This research contributes to the understanding of the interface and the feasible strategy for the practical application of the Zn anode.

Tellurium with Reversible Six-Electron Transfer Chemistry for High-Performance Zinc Batteries.

Chalcogens, especially tellurium (Te), as conversion-type cathodes possess promising prospects for zinc batteries (ZBs) with potential rich valence supply and high energy density. However, the conversion reaction of Te is normally restricted to the Te2-/Te0 redox with a low voltage plateau at ∼0.59 V (vs Zn2+/Zn) rather than the expected positive valence conversion of Te0 to Ten+, inhibiting the development of Te-based batteries toward high output voltage and energy density. Herein, the desired reversible Te2-/Te0/Te2+/Te4+ redox behavior with up to six-electron transfer was successfully activated by employing a highly concentrated Cl--containing electrolyte (Cl- as strong nucleophile) for the first time. Three flat discharge plateaus located at 1.24, 0.77, and 0.51 V, respectively, are attained with a total capacity of 802.7 mAh g-1. Furthermore, to improve the stability of Ten+ products and enhance the cycling stability, a modified ionic liquid (IL)-based electrolyte was fabricated, leading to a high-performance Zn∥Te battery with high areal capacity (7.13 mAh cm-2), high energy density (542 Wh kgTe-1 or 227 Wh Lcathdoe+anode-1), excellent cycling performance, and a low self-discharge rate based on 400 mAh-level pouch cell. The results enhance the understanding of tellurium chemistry in batteries, substantially promising a remarkable route for advanced ZBs.

Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice.

Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of a SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN(103PFU) in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.

Impact damage reduction of woven composites subject to pulse current.

3D orthogonal woven composites are receiving increasing attention with the ever-growing market of composites. A current challenge for these materials' development is how to improve their damage tolerance in orthogonal and layer-to-layer structures under extreme loads. In this paper, a damage reduction strategy is proposed by combining structural and electromagnetic properties. An integrated experimental platform is designed combining a power system, a drop-testing machine, and data acquisition devices to investigate the effects of pulse current and impact force on woven composites. Experimental results demonstrate that pulse current can effectively reduce delamination damage and residual deformation. A multi-field coupled damage model is developed to analyze the evolutions of temperature, current and damage. Parallel current-carrying carbon fibers that cause yarns to be transversely compressed enhance the mechanical properties. Moreover, the microcrack formation and extrusion deformation in yarns cause the redistribution of local current among carbon fibers, and its interaction with the self-field produces an obvious anti-impact effect. The obtained results reveal the mechanism of damage reduction and provide a potential approach for improving damage tolerance of these composites.

Spider Silk-Inspired Binder Design for Flexible Lithium-Ion Battery with High Durability.

The development of flexible lithium-ion batteries (LIBs) imposes demands on energy density and high mechanical durability simultaneously. Due to the limited deformability of electrodes, as well as the flat and smooth surface of the metal current collectors, stable/durable/reliable contact between electrode materials and the current collectors remains a challenge, in particular, for electrodes with high loading mass and heavily deformed batteries. Binders play an essential role in binding particles of electrode materials and adhering them to current collectors. Herein, inspired by spider silk, a binder for flexible LIBs is developed, which equips a cross-linked supramolecular poly(urethane-urea) to the polyacrylic acid. The binder imparts super high elastic restorability originating from the meticulously engineered hydrogen-bonding segments as well as extraordinary adhesion. The developed binder provides excellent flexibility and intact electrode morphologies without disintegration even when the electrode is largely deformed, enabling a stable cycling and voltage output even when the batteries are put under tough dynamic deformation tests. The flexible LIBs exhibit a high energy density of 420 Wh L-1 , which is remarkably higher than reported numbers. The unique binder design is greatly promising and offers a valuable material solution for LIBs with high-loading mass and flexible designs.

Long-Lasting Zinc-Iodine Batteries with Ultrahigh Areal Capacity and Boosted Rate Capability Enabled by Nickel Single-Atom Electrocatalysts.

Zinc-iodine (Zn-I2) batteries have garnered significant attention for their high energy density, low cost, and inherent safety. However, several challenges, including polyiodide dissolution and shuttling, sluggish iodine redox kinetics, and low electrical conductivity, limit their practical applications. Herein, we designed a highly efficient electrocatalyst for Zn-I2 batteries by uniformly dispersing Ni single atoms (NiSAs) on hierarchical porous carbon skeletons (NiSAs-HPC). In situ Raman analysis revealed that the conversion of soluble polyiodides (I3- and I5-) was significantly accelerated using NiSAs-HPC because of the remarkable electrocatalytic activity of NiSAs. The resulting Zn-I2 batteries with NiSAs-HPC/I2 cathodes delivered exceptional rate capability (121 mAh g-1 at 50 C), and ultralong cyclic stability (over 40 000 cycles at 50 C). Even under 11.6 mg cm-2 iodine, Zn-I2 batteries still exhibited an impressive cyclic stability with a capacity retention of 93.4% and 141 mAh g-1 after 10 000 cycles at 10 C.

Distinct chemistry between Zn and Li at varied temperature.

The operating temperature of batteries is an essential consideration in actual applications. Understanding the temperature dependence is conducive to battery design. The experience in lithium-ion batteries (LIBs) indicates that the dendrite issue is exacerbated at lower temperatures and suppressed at higher temperatures. In this study, we revealed the dendrite evolution in aqueous rechargeable zinc-based batteries (RZBs), for which the opposite temperature dependence was observed. Detailed investigations elucidate that the degree of matching of the interface reaction rate and ion diffusivity, together with side reactions, are the key factors that determine the cycling performance. The different properties of organic and aqueous electrolytes result in a reversed temperature dependence. We further conducted a detailed investigation of hybrid electrolytes (organic and aqueous) for balancing the ion diffusivity and side reactions to broaden the working temperature window for RZBs. This work reveals a completely opposite temperature dependence for LIBs and RZBs and discloses the underlying mechanism, reminding one of the differences between LIBs and RZBs in many aspects.

Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome.

Hearing loss is the leading sensory deficit, affecting ~ 5% of the population. It exhibits remarkable heterogeneity across 223 genes with 6328 pathogenic missense variants, making deafness-specific expertise a prerequisite for ascribing phenotypic consequences to genetic variants. Deafness-implicated variants are curated in the Deafness Variation Database (DVD) after classification by a genetic hearing loss expert panel and thorough informatics pipeline. However, seventy percent of the 128,167 missense variants in the DVD are "variants of uncertain significance" (VUS) due to insufficient evidence for classification. Here, we use the deep learning protein prediction algorithm, AlphaFold2, to curate structures for all DVD genes. We refine these structures with global optimization and the AMOEBA force field and use DDGun3D to predict folding free energy differences (∆∆GFold) for all DVD missense variants. We find that 5772 VUSs have a large, destabilizing ∆∆GFold that is consistent with pathogenic variants. When also filtered for CADD scores (> 25.7), we determine 3456 VUSs are likely pathogenic at a probability of 99.0%. Of the 224 genes in the DVD, 166 genes (74%) exhibit one or more missense variants predicted to cause a pathogenic change in protein folding stability. The VUSs prioritized here affect 119 patients (~ 3% of cases) sequenced by the OtoSCOPE targeted panel. Approximately half of these patients previously received an inconclusive report, and reclassification of these VUSs as pathogenic provides a new genetic diagnosis for six patients.

Circ_0078607 increases platinum drug sensitivity via miR-196b-5p/GAS7 axis in ovarian cancer.

Platinum-based chemotherapy is one of the predominant strategies for treating ovarian cancer (OC), however, platinum resistance greatly influences the therapeutic effect. Circular RNAs (circRNAs) have been found to participate in the pathogenesis of platinum resistance. Our aim was to explore the involvement of circ_0078607 in OC cell cisplatin (DDP) resistance and its potential mechanisms. Circ_0078607, miR-196b-5p, and growth arrest-specific 7 (GAS7) levels were assessed by qPCR. Circ_0078607 stability was assessed by ribonuclease R digestion and actinomycin D treatment. Cell viability of various conic of DDP treatment was measured by CCK-8. The cell proliferation was determined by CCK-8 and colony formation assay. Western blotting was performed for determining GAS7, ABCB1, CyclinD1 and Bcl-2 protein levels. The direct binding between miR-196b-5p and circ_0078607 or GAS7 was validated by dual-luciferase reporter and RIP assay. DDP resistance in vivo was evaluated in nude mice. Immunohistochemistry staining for detecting Ki67 expression in xenograft tumours. Circ_0078607 and GAS7 was down-regulated, but miR-196b-5p was up-regulated in OC samples and DDP-resistant cells. Overexpression of circ_0078607 inhibited DDP resistance, cell growth and induced apoptosis in DDP-resistant OC cells. Mechanistically, circ_0078607 sequestered miR-196b-5p to up-regulate GAS7. MiR-196b-5p mimics reversed circ_0078607 or GAS7 overexpression-mediated enhanced sensitivity. Finally, circ_0078607 improved the sensitivity of DDP in vivo. Circ_0078607 attenuates DDP resistance via miR-196b-5p/GAS7 axis, which highlights the therapeutic potential of circ_0078607 to counter DDP resistance in OC.