Coexistence of Ferromagnetism and Superconductivity at KTaO3 Heterointerfaces.

The coexistence of superconductivity and ferromagnetism is a long-standing issue in superconductivity due to the antagonistic nature of these two ordered states. Experimentally identifying and characterizing novel heterointerface superconductors that coexist with magnetism presents significant challenges. Here, we report the observation of two-dimensional long-range ferromagnetic order in a KTaO3 heterointerface superconductor, showing the coexistence of superconductivity and ferromagnetism. Remarkably, our direct current superconducting quantum interference device measurements reveal an in-plane magnetization hysteresis loop persisting above room temperature. Moreover, first-principles calculations and X-ray magnetic circular dichroism measurements provide decisive insights into the origin of the observed robust ferromagnetism, attributing it to oxygen vacancies that localize electrons in nearby Ta 5d states. Our findings suggest KTaO3 heterointerfaces as time-reversal symmetry breaking superconductors, injecting fresh momentum into the exploration of the intricate interplay between superconductivity and magnetism enhanced by the strong spin-orbit coupling inherent to the heavy Ta in 5d orbitals.

A Statovirus-like virus from respiratory tracts of patients, China.

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.

Analyzing microbial community and volatile compound profiles in the fermentation of cigar tobacco leaves.

Variations in industrial fermentation techniques have a significant impact on the fermentation of cigar tobacco leaves (CTLs), consequently influencing the aromatic attributes of the resulting cigars. The entire fermentation process of CTLs can be categorized into three distinct phases: phase 1 (CTLs prior to moisture regain), phase 2 (CTLs post-moisture regain and pile fermentation), and phase 3 (CTLs after fermentation and drying). These phases were determined based on the dynamic changes in microbial community diversity. During phase 2, there was a rapid increase in moisture and total acid content, which facilitated the proliferation of Aerococcus, a bacterial genus capable of utilizing reducing sugars, malic acid, and citric acid present in tobacco leaves. In contrast, fungal microorganisms exhibited a relatively stable response to changes in moisture and total acid, with Aspergillus, Alternaria, and Cladosporium being the dominant fungal groups throughout the fermentation stages. Bacterial genera were found to be more closely associated with variations in volatile compounds during fermentation compared to fungal microorganisms. This association ultimately resulted in higher levels of aroma components in CTLs, thereby improving the overall quality of the cigars. These findings reinforce the significance of industrial fermentation in shaping CTL quality and provide valuable insights for future efforts in the artificial regulation of secondary fermentation in CTLs. KEY POINTS: • Industrial fermentation processes impact CTLs microbial communities. • Moisture and total acid content influence microbial community succession in fermentation. • Bacterial microorganisms strongly influence CTLs' aldehyde and ketone flavors over fungi.

Correlation study on microbial communities and volatile flavor compounds in cigar tobacco leaves of diverse origins.

To elucidate the significant influence of microorganisms on geographically dependent flavor formation by analyzing microbial communities and volatile flavor compounds (VFCs) in cigar tobacco leaves (CTLs) obtained from China, Dominica, and Indonesia. Microbiome analysis revealed that the predominant bacteria in CTLs were Staphylococcus, Aerococcus, Pseudomonas, and Lactobacillus, while the predominant fungi were Aspergillus, Wallemia, and Sampaiozyma. The microbial communities of CTLs from different origins differed to some extent, and the diversity and abundance of bacteria were greater than fungi. Metabolomic analysis revealed that 64 VFCs were identified, mainly ketones, of which 23 VFCs could be utilized to identify the geographical origins of CTLs. Sixteen VFCs with OAV greater than 1, including cedrol, phenylacetaldehyde, damascone, beta-damascone, and beta-ionone, play important roles in shaping the flavor profile of CTLs from different origins. Combined with the correlation analysis, bacterial microorganisms were more closely related to key VFCs and favored a positive correlation. Bacillus, Vibrio, and Sphingomonas were the main flavor-related bacteria. The study demonstrated that the predominant microorganisms were essential for the formation of key flavor qualities in CTLs, which provided a theoretical reference for flavor control of CTLs by microbial technology. KEY POINTS: • It is the high OAV VFCs that determine the flavor profile of CTLs. • The methylerythritol phosphate (MEP) pathway and the carotenoid synthesis pathway are key metabolic pathways for the formation of VFCs in CTLs. • Microbial interactions influence tobacco flavor, with bacterial microorganisms contributing more to the flavor formation of CTLs.

Evaluate the Influencing Factors of Congruency of the First Metatarsophalangeal Joint in Hallux Valgus Based on Weightbearing CT.

The purpose of this study was to explore the difference between congruency and incongruency of the first metatarsophalangeal (MTP) joint in hallux valgus using weightbearing CT (WBCT) and to identify the risk factors for incongruency. From January 2019 to January 2021, WBCT scans were retrospectively analyzed for 110 (191 feet) consecutive patients. According to whether the metatarsal articular surface and phalanx articular surface were parallel, they were divided into congruency (73 feet) and incongruency groups (118 feet). The age, intermetatarsal angle (IMA), hallux valgus angle (HVA), distal metatarsal articular surface angle (DMAA), first metatarsal coronal pronation angle (α angle), tibial sesamoid 7 positions (TSP), and tibial sesamoid coronal grading (TSCG) were compared between the 2 groups. Binary logistic regression was used to analyze the influencing factors of incongruency. Receiver operating characteristic (ROC) curve analysis was applied to determine the cutoff value. There were significant differences in IMA, HVA, DMAA, α angle, age, TSP, and TSCG between congruency and incongruency groups (p < .05). Binary logistic regression analysis showed that TSCG, HVA, α angle were the influencing factors of incongruency. ROC curve analysis demonstrated that the cutoff values for incongruency were 1 position for TSCG (sensitivity: 0.835; specificity: 0.884) with the area under curve (AUC) of 0.892, 30° (sensitivity: 0.795; specificity: 0.812) for HVA with the AUC of 0.878, and 24° (sensitivity: 0.530; specificity: 0.797) for α angle with the AUC of 0.686. Incongruency of the first MTP joint indicated a more severe hallux valgus, and was associated with increased HVA, α angle, and TSCG.

High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence.

Identification of unique and specific biomarkers to better detect and quantify senescent cells remains challenging. By a global proteomic profiling of senescent human skin BJ fibroblasts induced by ionizing radiation (IR), the cellular level of pregnancy zone protein (PZP), a presumable pan-protease inhibitor never been linked to cellular senescence before, was found to be decreased by more than 10-fold, while the level of PZP in the conditioned medium was increased concomitantly. This observation was confirmed in a variety of senescent cells induced by IR or DNA-damaging drugs, indicating that high-level secretion of PZP is a novel senescence-associated secretory phenotype. RT-PCR examination verified that the transcription of the PZP gene is enhanced in various cells at senescence or upregulated following DNA damage treatment in a p53-independent manner. Moreover, pretreatment with late pregnancy serum containing a high level of PZP led to inhibition of doxorubicin-induced senescence in A549 cells, and depletion of PZP in the pregnancy serum could enhance such inhibition. Finally, the addition of immuno-precipitated PZP complexes into tissue culture attenuated the growth of A549 cells and promoted the spontaneous senescence. Therefore, we revealed that high-level secretion of PZP is a novel and unique feature associated with DNA damage-induced senescence, and secreted PZP is a positive regulator of cellular senescence, particularly during the late stage of gestation.

Genomic Characteristics of Emerging Intraerythrocytic Anaplasma capra and High Prevalence in Goats, China.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

AMPK/mTOR/p70S6K axis prevents apoptosis of Porphyromonas gingivalis-infected gingival epithelial cells via BadSer136 phosphorylation.

Epithelial disruption is the initiation of most infectious disease. Regulation of epithelium apoptosis may play a key role in balance the survival competition between resident bacteria and host cells. The role of the mTOR/p70S6K pathway in preventing apoptosis of human gingival epithelial cells (hGECs) infected with Porphyromonas gingivalis (Pg) was investigated in order to further understand the survival strategy of the epithelial cells in during Pg infecting. hGECs was challenged with Pg for 4, 12, and 24 h. Additionally, hGECs was pretreated with LY294002 (PI3K signaling inhibitor) or Compound C (AMPK inhibitor) for 12 h and exposed them to Pg for 24 h. Subsequently, apoptosis was detected using flow cytometry, and expression and activity of Bcl-2, Bad, Bax, PI3K, AKT, AMPK, mTOR, and p70S6K proteins were analyzed using western blotting. Pg-infecting did not increase apoptosis of hGECs; but the expression ratio of Bad to Bcl-2 was increased after infecting. In contrast, BadSer136 phosphorylation was promoted, accompanied by a significant reduction of mTOR/p70S6K and PI3K/AKT signaling, along with the upregulation of AMPKThr172 signaling. Morrover, the PI3K inhibitor LY294002 promoted Pg-mediated reduction of mTOR/p70S6K expression, and the increase of AMPK signaling and BadSer136 phosphorylation rate, eventually decreasing apoptosis. While Compound C inhibited Pg-mediated activation of AMPK and downregulation of mTOR/p70S6K signaling, significantly reduced the BadSer136 phosphorylation rate, thereby increasing apoptosis. Thus, hGECs prevent apoptosis via an inherent cellular-homeostasis, pro-survival mechanism during Pg infection, the AMPK/mTOR/p70S6K pathway helps prevent apoptosis in hGECs infected with Pg by regulating BadSer136 phosphorylation.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

The influence of verapamil on the pharmacokinetics of the pan-HER tyrosine kinase inhibitor neratinib in rats: the role of P-glycoprotein-mediated efflux.

Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has been approved for the treatment of HER2-positive (HER2+) early-stage and brain metastatic breast cancer. Thus far, the pharmacology effects and pharmacodynamics of neratinib have been well studied. However, the disposition of neratinib and its influencing factors in vivo remain unclear. P-glycoprotein (P-gp), one of the most extensively studied transporters, substantially restricts penetration of drugs into the body or deeper compartments (i.e., blood-brain barrier, BBB), regarding drug resistance and drug-drug interactions. Thereby, the aim of this study was to investigate the influence of verapamil (a P-gp inhibitor) on the pharmacokinetics of neratinib in rats. Here, we have established a high specific, selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify plasma concentrations of neratinib in rats. Pharmacokinetic results showed that verapamil significantly increased the system exposure of neratinib, as Cmax increased by 2.09-fold and AUC0-t increased by 1.64-fold, respectively. Additionally, the in vitro transport of neratinib was evaluated using Madin-Darby canine kidney II (MDCK II) and human MDR1 gene overexpressed MDCK (MDCK-MDR1) cell line models. As a result, the net flux ratio was over than 2 and decreased over 50% by verapamil, suggesting that neratinib was a substrate of P-gp. Hence, our findings have highlighted the important role of P-gp in the system exposure of neratinib in vivo, and drug-drug interaction should be considered when coadministration of P-gp inhibitors with neratinib. These findings may support the further clinical development and application of neratinib.

Prussian blue analogues-derived zero valent iron to efficiently activate peroxymonosulfate for phenol degradation triggered via reactive oxygen species and high-valent iron-oxo complexes.

It is of great significance to develop the effective technique to treat phenol-containing wastewater. Herein, Fe-based prussian blue analogues-derived zero valent iron (ZVI) was successfully synthesized by one-step calcination method. Owing to high specific surface area and rich active sites, ZVI-2 possessed excellent performance in charge transfer. Notably, in comparison with conventional ZVI and Fe2+, ZVI-2 can effectively activate peroxymonosulfate (PMS) for achieving rapid degradation of phenol, and the highest removal efficiency of phenol reached 94.9% within 24 min. More importantly, developed ZVI-2/PMS oxidation system with good stability displayed strong anti-interference capability. Interestingly, Fe0 loaded on the surface of ZVI-2 can efficiently break the O-O bond of PMS to generate reactive oxygen species (i.e., SO4•-, OH•, O2•- and 1O2). As main adsorption sites of PMS, the existence of oxygen vacancy promote the formation of high-valent transition metal complexes (namely ZVI-2≡Fe4+=O). Under the combined action of reactive oxygen species and ZVI-2≡Fe4+=O, phenol can be eventually degraded into CO2 and H2O. The possible degradation pathways of phenol were also investigated. Furthermore, proposed ZVI-2/PMS oxidation system displayed great potential for application in the field of wastewater treatment. All in all, current work provided a valuable reference for design and application of Fe-based catalysts in PS-AOPs.

Lyonensinols A - C, 24-Norursane-Type Triterpenoids from the Twigs and Leaves of Lyonia doyonensis and Their Potential Anti-inflammatory and PTP1B Inhibitory Activities.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis. An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4 - 9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis-p-coumaroyl group.

miR-148a-3p regulates proliferation and apoptosis of idiopathic gingival fibroma by targeting NPTX1.

OBJECTIVE: Idiopathic gingival fibromatosis (IGF) is a rare heterogeneous disease that results in the progressive and diffuse hyperplasia of gingival tissues. MicroRNAs are implicated in the development and progression of various tumors. The present study aimed to explore the potential roles and mechanisms of miR-148a-3p in IGF. METHODS: Gingival fibroblasts (GFs) were transfected with miR-148a-3p mimics, miR-148a-3p inhibitors, or siNPTX1, and then, the proliferation and apoptosis of GFs and the expression of related genes were evaluated using Cell Counting Kit-8 assays, 5-ethynyl-2'-deoxyuridine assays, flow cytometry, reverse transcription-quantitative polymerase chain reaction, and western blot analysis, respectively. RESULTS: miR-148a-3p was highly expressed in GFs of IGF (IGF-GFs) as compared with normal GFs (N-GFs). Overexpression of miR-148a-3p promoted the proliferation and inhibited the apoptosis of N-GFs, whereas downregulation of miR-148a-3p had the opposite effect in IGF-GFs. Knockdown of NPTX1 reversed miR-148a-3p-mediated effects in IGF-GFs. Dual-luciferase reporter assay confirmed that NPTX1 is a direct target of miR-148a-3p. CONCLUSION: These findings identify that miR-148a-3p could regulate cell proliferation and apoptosis by targeting NPTX1, providing new insights for the further study of the molecular mechanism and treatment of IGF.

Impact of medication therapy management (MTM) service model on multi-morbidity (MMD) patients with hypertension: a pilot RCT.

BACKGROUND: This study explored the impact of MTM service on MMD patients with hypertension. METHODS: A total of 120 MMD inpatients from September to November 2019 were received and randomly divided into intervention group and control group. General services for noninfectious chronic diseases were given to the control group, while a standard MTM service was given to the intervention group. Patients' blood pressure, EQ-5D utility value, readmission rate, drug-related problems, and average daily medication therapy cost were compared between the two groups and within the groups. This was done at the initial admission phase and in the first, third, sixth, and twelfth months after discharge. RESULTS: The intervention group had significantly lower blood pressure and average daily medication therapy cost 12 months after discharge compared to the control group (systolic blood pressure: P = 0.023, diastolic blood pressure: P < 0.001, average daily medication therapy cost: P = 0.049); the number of DRPs decreased in both groups 12 months after discharge; the number of DRPs solved in the intervention group in the third, sixth and twelfth months after discharge were statistically higher compared with that in the control group (P = 0.013, P = 0.012, P = 0.001); there was no significant difference in the EQ-5D utility value and readmission rate between the two groups (P > 0.05). CONCLUSIONS: MTM implementation in MMD patients can improve health outcomes and reduce healthcare-related costs among MMD patients. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR2200065111, date of registration: October 28, 2022.

Regulation of gut bacteria in silkworm (Bombyx mori) after exposure to endogenous cadmium-polluted mulberry leaves.

Soil cadmium (Cd) pollution presents a severe pollution burden to flora and fauna due to its non-degradability and transferability. The Cd in the soil is stressing the silkworm (Bombyx mori) out through a soil-mulberry-silkworm system. The gut microbiota of B.mori are reported to shape host health. However, earlier research had not reported the effect of endogenous Cd-polluted mulberry leaves on the gut microbiota of B.mori. In the current research, we compared the phyllosphere bacteria of endogenous Cd-polluted mulberry leaves at different concentrations. The investigation of the gut bacteria of B.mori fed with the mulberry leaves was done to evaluate the impact of endogenous Cd- polluted mulberry leaves on the gut bacteria of the silkworm. The results revealed a dramatic change in the gut bacteria of B.mori whereas, the changes in the phyllosphere bacteria of mulberry leaves in response to an increased Cd concentration were insignificant. It also increased the α-diversity and altered the gut bacterial community structure of B. mori. A significant change in the abundance of dominant phyla of gut bacteria of B.mori was recorded. At the genus level, the abundance of Enterococcus, Brachybacterium and Brevibacterium group related to disease resistance, and the abundance of Sphingomonas, Glutamicibacter and Thermus related to metal detoxification was significantly increased after Cd exposure. Meanwhile, there was a significant decrease in the abundance of the pathogenic bacteria Serratia and Enterobacter. The results demonstrated that endogenous Cd-polluted mulberry leaves caused perturbations in the gut bacterial composition of B.mori, which may driven by Cd content rather than phyllosphere bacteria. A significant variation in the specific bacterial community indicated the adaptation of B. mori gut for its role in heavy metal detoxification and immune function regulation. The results of this study help to understand the bacterial community associated with endogenous Cd-polluted resistance in the gut of B.mori, which proves to be a novel addition in describing its response in activating the detoxification mechanism and promoting its growth and development. This research work will help to explore the other mechanisms and microbiota associated with the adaptations to mitigate the Cd pollution problems.

Safety and efficacy of intra-articular injection of platelet-rich plasma for the treatment of ankle osteoarthritis: a systematic review and meta-analysis.

PURPOSE: To evaluate the safety and efficacy of platelet-rich plasma (PRP) intra-articular injective treatments for ankle osteoarthritis (OA). METHODS: A systematic literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in PubMed, Scopus, Embase, Google Scholar, and the Cochrane library until May 2022. Both randomized and non-randomized studies were included with the assessment of the risk of bias. We recorded the participant's age, gender, type of PRP, injection volume, the kit used, and activating agent. We subsequently assessed the short-term and long-term efficacy of PRP using the functional scores and visual analog scale (VAS). RESULTS: We included four studies with a total of 127 patients, with a mean age of 56.1 years. 47.2% were male (60/127), according to eligibility criteria. There were three cohort studies and one randomized controlled trial (RCT) study, and no study reported severe adverse events. All included studies used the Leukocyte-poor PRP. Short-term follow-up results suggested significant improvement of the American Orthopaedic Foot and Ankle Society (AOFAS) score in the PRP injection group compared to the control group (n = 87 patients; MD: 6.94 [95% CI: 3.59, 10.29]; P < 0.01). Consistently, there was a statistical difference in AOFAS score between PRP injection and control groups in the final follow-up (≥ 6 months) (n = 87 patients; MD: 9.63 [95% CI: 6.31, 12.94]; P < 0.01). Furthermore, we found a significant reduction in VAS scores in the PRP groups at both the short-term follow-up (n = 59 patients; MD, - 1.90 [95% CI, - 2.54, - 1.26]; P < 0.01) and the ≥ six months follow-up (n = 79 patients; MD, - 3.07 [95% CI, - 5.08, - 1.05]; P < 0.01). The improvement of AOFAS and VAS scores at ≥ six months follow-up reached the minimal clinically important difference (MCID). Nevertheless, the treatment effect of AOFAS and VAS scores offered by PRP at short-term follow-up did not exceed the MCID. Substantial heterogeneity was reported at the ≥ six months follow-up in VAS scores (I2: 93%, P < 0.01). CONCLUSION: This meta-analysis supports the safety of PRP intra-articular injection for ankle OA. The improvements of AOFAS and VAS scores in the PRP group at short-term follow-up do not exceed the MCID to be clinically significant. PRP injection provides significant improvement of AOFAS score and reduced pain at ≥ six months follow-up. The efficacy of PRP should be interpreted with caution regarding the high heterogeneity and the scarcity of available literature, which urges large-scale RCTs with longer follow-up to confirm the potential efficacy of PRP injection for ankle OA.

Regulation of potential denitrification rates in sediments by microbial-driven elemental coupled metabolisms.

Microbial driven coupled processes between denitrification and methane/sulfur metabolism play a very substantial role in accelerating nitrogen removal in river sediments. Until now, little is known about how element coupling processes alter nitrogen metabolism by the microbial functional communities. The primary objective of this research was to clarify the contributory role of microbial-mediated coupled processes in controlling denitrification. Specifically, the study sought to identify the key bioindicators (or metabolic pathway) for preferably regulating and predicting potential denitrification rate (PDR). Here, a total of 40 sediment samples were collected from the inflow rivers of Chaohu Lake under nitrogen stress. The results revealed the ecological importance of methanogens and sulfate reducing bacteria in the microbial interaction network. Correlations between quantitative or predicted genes showed that the methanogenic gene (mcrA) was synergistic with denitrifying genes, further unraveling that the key role of methanogenesis in denitrification process for facilitating nitrogen removal. The PDR of sediments ranged from 0.03 to 133.21 µg N·g-1·h-1. The study uncovered specific environmental factors (NH4+ and OM) and microbial indicators (nosZ, mcrA, Paracoccus, Thauera, Methanobrevibacter and Desulfomicrobium) as potential contributors to the variations in PDR. Structural Equation Model (SEM) analysis revealed a significant direct effect of NH4+ on PDR, evidenced by a standardized coefficient (λ) of 0.77 (P < 0.001). Additionally, the findings also emphasized the salient role of methanogens (Methanobrevibacter) and methanogenic gene (mcrA) in indicating PDR. The research's aforementioned findings shed light on the substantial consequences of methanogenesis on nitrogen metabolism in coupled processes, enabling improved control of nitrogen pollution in river sediments. This study provided fresh perspectives on the effects of multiple functional taxa on denitrification, and reinforces the significance of coupling processes for nitrogen removal.

Changes in the subtalar joint alignment after supramalleolar osteotomy for varus ankle arthritis.

BACKGROUND: The subtalar joint may compensate for tibio-talar deformity, but what would happen to the joint after the deformity was corrected is not well known. Supramalleolar osteotomy (SMOT) is an effective procedure for the treatment of varus deformity of ankle arthritis. The objective of this study was to investigate the subtalar joint alignment pre and postoperatively following SMOT, and the factors which influenced the alignment of the subtalar joint. METHODS: Thirty-one patients with varus ankle arthritis (Takakura stage 2, 3a and 3b) who were treated using SMOT were retrospectively reviewed. The subtalar and ankle joint alignment was measured on weightbearing radiograph and weightbearing computerized tomography (WBCT). RESULTS: The foot and ankle offset (FAO), tibial articular surface angle (TAS), tibio-talar surface angle (TTS), and subtalar vertical angle (SVA) were significantly corrected (P＜0.05). The subtalar inclination angle (SIA) decreased in 19 patients and increased in the other 12 cases after the SMOT (P＜0.001). The shift of subtalar joint (ΔSIA) showed an inverse correlation with the preoperative FAO (P＜0.001, r = -0.621). CONCLUSIONS: The shift of subtalar joint after SMOT could maintain the neutral position of the hindfoot and showed a negative correlation with the preoperative FAO. The ΔSIA was greater in the severer preoperative hindfoot deformity. LEVEL OF EVIDENCE: Level IV, case series.

Subchondral bone cysts remodel after correction of varus deformity in ankle arthritis.

BACKGROUND: Subchondral bone cysts (SBCs) of the talus are frequently observed in ankle osteoarthritis (OA). It is unclear whether the cysts need direct treatment after correction of the varus deformity in ankle OA. The purpose of this study is to investigate the incidence of SBCs and the change after supramalleolar osteotomy (SMOT). METHODS: Thirty-one patients treated by SMOT were retrospectively reviewed, and 11 ankles had cysts preoperatively. After SMOT without management of the cysts, the evolution of cysts was evaluated on weightbearing computerized tomography (WBCT). The American Orthopaedic Foot and Ankle Society (AOFAS) clinical ankle-hindfoot scale and a visual analog scale (VAS) were compared. RESULTS: At baseline, the average cyst volume was 65.86 ± 60.53 mm3. The number and volume of cysts were reduced dramatically (P＜.05), and the cysts vanished in 6 ankles after the SMOT. The VAS and AOFAS scores improved significantly after SMOT (P＜.001), there was no significant difference between ankles with cysts and without cysts. CONCLUSIONS: The SMOT alone without direct treatment of the SBCs led to a decrease in the number and volume of SBCs in varus ankle OA. LEVEL OF EVIDENCE: Level IV, case series.

Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma.

BACKGROUND: Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. METHODS: Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, ß-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. RESULTS: Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent ß-catenin stabilization and nuclear translocation. Nuclear ß-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. CONCLUSIONS: This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma. Video Abstract.