CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes.

Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1ß, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.

Effects of hypoxic compound exercise to promote HIF-1α expression on cardiac pumping function, sleep activity behavior, and exercise capacity in Drosophila.

Alteration of HIF-1α expression levels under hypoxic conditions affects the sequence of its downstream target genes thereby producing different effects. In order to investigate whether the effect of hypoxic compound exercise (HE) on HIF-1α expression alters cardiac pumping function, myocardial structure, and exercise capacity, we developed a suitable model of hypoxic exercise using Drosophila, a model organism, and additionally investigated the effect of hypoxic compound exercise on nocturnal sleep and activity behavior. The results showed that hypoxic compound exercise at 6% oxygen concentration for five consecutive days, lasting 1 h per day, significantly improved the cardiac stress resistance of Drosophila. The hypoxic complex exercise promoted the whole-body HIF-1α expression in Drosophila, and improved the jumping ability, climbing ability, moving speed, and moving distance. The expression of HIF-1α in the heart was increased after hypoxic exercise, which made a closer arrangement of myofilaments, an increase in the diameter of cardiac tubules, and an increase in the pumping function of the heart. The hypoxic compound exercise improved the sleep quality of Drosophila by increasing its nocturnal sleep time, the number of deep sleeps, and decreasing its nocturnal awakenings and activities. Therefore, we conclude that hypoxic compound exercise promoted the expression of HIF-1α to enhance the exercise capacity and heart pumping function of Drosophila, and improved the quality of sleep.

Broadband and strong visible-light-absorbing cuprous sensitizers for boosting photosynthesis.

Rational construction of broadband and strong visible-light-absorbing (BSVLA) earth-abundant complexes is of great importance for efficient and sustainable solar energy utilization. Herein, we explore a universal Cu(I) center to couple with multiple strong visible-light-absorbing antennas to break the energy level limitations of the current noble-metal complexes, resulting in the BSVLA nonprecious complex (Cu-3). Systematic investigations demonstrate that double "ping-pong" energy-transfer processes in Cu-3 involving resonance energy transfer and Dexter mechanism enable a BSVLA between 430 and 620 nm and an antenna-localized long-lived triplet state for efficient intermolecular electron/energy transfer. Impressively, Cu-3 exhibited an outstanding performance for both energy- and electron-transfer reactions. Pseudo-first-order rate constant of photooxidation of 1,5-dihydroxynaphthalene with Cu-3 can achieve a record value of 190.8 × 10-3 min-1 among the molecular catalytic systems, over 30 times higher than that with a noble-metal photosensitizer (PS) [Ru(bpy)3]2+. These findings pave the way to develop BSVLA earth-abundant PSs for boosting photosynthesis.

Comparative genomics reveals ample evidence to Ganoderma sinense cultivars for molecular identification and new FIP exploration.

The first dikaryotic genome of Ganoderma cultivar Zizhi S2 (56.76 Mb, 16,681 genes) has been sequenced recently. 98.15% of complete BUSCOs were recovered in this genome assembly and high-confidence annotation rate improved to 91.41%. Collinearity analysis displayed the nuclear genome were 80.2% and 93.84% similar to reference genome of G. sinense at nucleotide and amino acid levels, which presented 8,521 core genes and 880 unique orthologous gene groups. Among that, at least six functional genes (tef1-α, ß-tubulin, rpb2, CaM, Mn-SOD and VeA) and a newly discovered fip gene were highly similar 99.27% ∼100% to those in reference genome. And the mt-LSU, mt-SSU and 13 PCGs in their mitogenome were also highly conserved with 99.27%-99.87% and 99.08%-100% identity, respectively. So that, this cultivar Zizhi S2 is confirmed conspecific with Ganoderma sinense (NCBI: txid1077348). The new fip gene (MN635280.1_336bp) existing a novel mutation which can be reflected on the phylogenetic tree and 3-dimensional model topology structure.

A Robust Pyro-phototronic Route to Markedly Enhanced Photocatalytic Disinfection.

Photocatalysis offers a direct, yet robust, approach to eradicate pathogenic bacteria. However, the practical implementation of photocatalytic disinfection faces a significant challenge due to low-efficiency photogenerated carrier separation and transfer. Here, we present an effective approach to improve photocatalytic disinfection performance by exploiting the pyro-phototronic effect through a synergistic combination of pyroelectric properties and photocatalytic processes. A set of comprehensive studies reveals that the temperature fluctuation-induced pyroelectric field promotes photoexcited carrier separation and transfer and thus facilitates the generation of reactive oxygen species and ultimately enhances photocatalytic disinfection performance. It is worth highlighting that the constructed film demonstrated an exceptional antibacterial efficiency exceeding 95% against pathogenic bacteria under temperature fluctuations and light irradiation. Moreover, the versatile modulation role of the pyro-phototronic effect in boosting photocatalytic disinfection was corroborated. This work paves the way for improving photocatalytic disinfection efficiency by harnessing the synergistic potential of various inherent material properties.

Multi-cohort validation of Ascore: an anoikis-based prognostic signature for predicting disease progression and immunotherapy response in bladder cancer.

Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions. Through consensus clustering, we categorized patients from the TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences in survival outcome, clinical features, tumor immune environment (TIME), and potential ICIs response were observed between clusters. We then formulated a four-gene signature, termed "Ascore", to encapsulate this gene expression pattern. The Ascore was found to be closely associated with survival outcome and served as an independent prognosticator in both the TCGA-BLCA cohort and the IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) for bladder cancer immunotherapy response compared to biomarkers like TMB and PD-L1. Finally, we evaluated Ascore's independent prognostic performance as a non-invasive biomarker in our clinical cohort (Gulou-Cohort1) using circulating tumor cells detection, achieving an AUC of 0.803. Another clinical cohort (Gulou-Cohort2) consisted of 40 patients undergoing neoadjuvant anti-PD-1 treatment was also examined. Immunohistochemistry of Ascore in these patients revealed its correlation with the pathological response to bladder cancer immunotherapy (P = 0.004). Impressively, Ascore (AUC = 0.913) surpassed PD-L1 (AUC = 0.662) in forecasting immunotherapy response and indicated better net benefit. In conclusion, our study introduces Ascore as a novel, robust prognostic biomarker for bladder cancer, offering a new tool for enhancing immunotherapy decisions and contributing to the tailored treatment approaches in this field.

Multiple Origins and Genomic Basis of Complex Traits in Sighthounds.

Sighthounds, a distinctive group of hounds comprising numerous breeds, have their origins rooted in ancient artificial selection of dogs. In this study, we performed genome sequencing for 123 sighthounds, including one breed from Africa, six breeds from Europe, two breeds from Russia, and four breeds and 12 village dogs from the Middle East. We gathered public genome data of five sighthounds and 98 other dogs as well as 31 gray wolves to pinpoint the origin and genes influencing the morphology of the sighthound genome. Population genomic analysis suggested that sighthounds originated from native dogs independently and were comprehensively admixed among breeds, supporting the multiple origins hypothesis of sighthounds. An additional 67 published ancient wolf genomes were added for gene flow detection. Results showed dramatic admixture of ancient wolves in African sighthounds, even more than with modern wolves. Whole-genome scan analysis identified 17 positively selected genes (PSGs) in the African population, 27 PSGs in the European population, and 54 PSGs in the Middle Eastern population. None of the PSGs overlapped in the three populations. Pooled PSGs of the three populations were significantly enriched in "regulation of release of sequestered calcium ion into cytosol" (gene ontology: 0051279), which is related to blood circulation and heart contraction. In addition, ESR1, JAK2, ADRB1, PRKCE, and CAMK2D were under positive selection in all three selected groups. This suggests that different PSGs in the same pathway contributed to the similar phenotype of sighthounds. We identified an ESR1 mutation (chr1: g.42,177,149 T > C) in the transcription factor (TF) binding site of Stat5a and a JAK2 mutation (chr1: g.93,277,007 T > A) in the TF binding site of Sox5. Functional experiments confirmed that the ESR1 and JAK2 mutation reduced their expression. Our results provide new insights into the domestication history and genomic basis of sighthounds.

A Holistic Additive Protocol Steers Dendrite-Free Zn(101) Orientational Electrodeposition.

Orientation guidance has shown its cutting edges in electrodeposition modulation to promote Zn anode stability toward commercialized standards. Nevertheless, large-scale orientational deposition is handicapped by the competition between Zn-ion reduction and mass transfer. Herein, a holistic electrolyte additive protocol is put forward via incorporating bio-derived dextrin molecules into a zinc sulfate electrolyte bath. Electrochemical tests in combination with molecular dynamics simulations demonstrate the alleviation of concentration polarization throughout accelerating Zn2+ diffusion and retarding their reduction. The predominant (101) texture on inert current collectors (i.e., Cu, Ti, and stainless steel) and (101)/(002) textures on Zn foils afford homogeneous electrical field distribution, which is contributed by the work difference to form the 2D nucleus and the adsorption of dextrin molecules, respectively. Consequently, the symmetric cell harvests a longevous cycling lifespan of over 4000 h at 0.5 mA cm-2 /0.5 mAh cm-2 while the Zn@Cu electrode sustains for 240 h at a high depth of discharge of 40%.

Simultaneous Biofilm Disruption, Bacterial Killing, and Inflammation Elimination for Wound Treatment Using Silver Embellished Polydopamine Nanoplatform.

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

Targeted gene sequencing reveals disparate genomic mutations between young and older adults in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated. METHODS: Clinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator. RESULTS: Our analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs. CONCLUSION: Our findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

The nature of crystal facet effect of TiO2-supported Pd/Pt catalysts on selective hydrogenation of cinnamaldehyde: electron transfer process promoted by interfacial oxygen species.

Supported noble metal nanocatalysts typically exhibit strong crystal plane dependent catalytic behavior, but their working mechanism is still unclear. Herein, using anatase TiO2 with well-exposed crystal facets of {101}, {100} and {001} as a prototype support, Pd- and Pt-based supported TiO2 nanocatalysts (TiO2-Pd and TiO2-Pt) were prepared by chemical reduction with NaBH4 as reducer, and they showed a distinct metal-dependent crystal facet effect in the selective hydrogenation of cinamaldehyde (CAL). For Pd-based nanocatalysts, most Pd species on the {100} plane of TiO2 are present in the oxidized form with positive charges and unexpectedly show higher reactivity than the Pd species in the zero-valence state on the {101} and {001} planes. On the contrary, Pt species on all three crystal planes of TiO2 show zero-valence state, with relatively low conversion, but much better selectivity for hydrogenation of a CO bond than Pd-based catalysts. Well-designed experiments manipulating the stability and type of surface oxygen species confirmed that the essence of the crystal facet effect of the catalyst support actually creates a unique nanoconfined interface at the molecular level to construct a surface p-band intermediate state (PBIS), which provides a new alternative channel for surface electron transfer and consequently accelerates the reaction kinetics.

A comparison of accuracy among different approaches of static-guided implant placement in patients treated with mandibular reconstruction: A retrospective study.

OBJECTIVE: This study aimed to evaluate the differences in the accuracy of immediate intraoral, immediate extraoral, and delayed dental implant placement with surgical guides (static computer-aided implant surgery) in patients treated with mandibular reconstruction. METHODS: This was a retrospective study. The patients were divided into three groups: immediate intraoral placement (IIO), immediate extraoral placement (IEO), and delayed placement (DEL). Four variables were used to compare the planned and actual implant positions: angular deviation, three-dimensional (3D) deviation at the entry point of the implant, 3D deviation at the apical point of the implant, and depth deviation. RESULTS: The angular deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. The 3D deviation at the entry point was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .01) groups. The 3D deviation at the apical point was significantly higher in the IIO group than in the IEO (p < .01) and DEL (p < .01) groups. The depth deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. There was no statistical difference between the IEO and DEL group in angular and 3D deviation. CONCLUSION: With surgical guides, among the different approaches for implant placement, delayed implant placement remains the most accurate approach for patients treated with mandibular reconstruction.

Feasibility and accuracy of noninvasive continuous hemoglobin monitoring using transesophageal photoplethysmography in porcine model.

BACKGROUND: Continuous and noninvasive hemoglobin (Hb) monitoring during surgery is essential for anesthesiologists to make transfusions decisions. The aim of this study was to investigate the feasibility and accuracy of noninvasive and continuous Hb monitoring using transesophageal descending aortic photoplethysmography (dPPG) in porcine model. METHODS: Nineteen landrace pigs, aged 3 to 5 months and weighing 30 to 50 kg, were enrolled in this study. A homemade oximetry sensor, including red (660 nm) and infrared (940 nm) lights, was placed in the esophagus for dPPG signal detection to pair with the corresponding reference Hb values (Hbi-STAT) measured by blood gas analysis. The decrease and increase changes in Hb concentration were achieved by hemodilution and transfusion. Metrics, including alternating current (AC), direct current (DC), and AC/DC for both red and infrared light were extracted from the dPPG signal. A receiver operating characteristic (ROC) curve was built to evaluate the performance of dPPG metrics in predicting the Hb "trigger threshold" of transfusion (Hb < 60 g/L and Hb > 100 g/L). Agreement and trending ability between Hb measured by dPPG (HbdPPG) and by blood gas analysis were analyzed by Bland-Altman method and polar plot graph. Error grid analysis was also performed to evaluate clinical significance of HbdPPG measurement. RESULTS: The dPPG signal was successfully detected in all of the enrolled experimental pigs, without the occurrence of a continuous loss of dPPG signal for 2 min during the entire measurement. A total of 376 pairs of dPPG signal and Hbi-STAT were acquired. ACred/DCred and ACinf/DCinf had moderate correlations with Hbi-STAT, and the correlation coefficients were 0.790 and 0.782, respectively. The areas under the ROC curve for ACred/DCred and ACinf/DCinf in predicting Hbi-STAT < 60 g/L were 0.85 and 0.75, in predicting Hbi-STAT > 100 g/L were 0.90 and 0.83, respectively. Bland-Altman analysis and polar plot showed a small bias (1.69 g/L) but a wide limit of agreement (-26.02-29.40 g/L) and a poor trend ability between HbdPPG and Hbi-STAT. Clinical significance analysis showed that 82% of the data lay within the Zone A, 18% within the Zone B, and 0% within the Zone C. CONCLUSION: It is feasible to establish a noninvasive and continuous Hb monitoring by transesophageal dPPG signal. The ACred/DCred extracted from the dPPG signal could provide a sensitive prediction of the Hb threshold for transfusion. The Hb concentration measured by dPPG signal has a moderate correlation with that measured by blood gas analysis. This animal study may provide an experimental basis for the development of bedside HbdPPG monitoring in the future.

Monocular Absolute Depth Estimation from Motion for Small Unmanned Aerial Vehicles by Geometry-Based Scale Recovery.

In recent years, there has been extensive research and application of unsupervised monocular depth estimation methods for intelligent vehicles. However, a major limitation of most existing approaches is their inability to predict absolute depth values in physical units, as they generally suffer from the scale problem. Furthermore, most research efforts have focused on ground vehicles, neglecting the potential application of these methods to unmanned aerial vehicles (UAVs). To address these gaps, this paper proposes a novel absolute depth estimation method specifically designed for flight scenes using a monocular vision sensor, in which a geometry-based scale recovery algorithm serves as a post-processing stage of relative depth estimation results with scale consistency. By exploiting the feature correspondence between successive images and using the pose data provided by equipped navigation sensors, the scale factor between relative and absolute scales is calculated according to a multi-view geometry model, and then absolute depth maps are generated by pixel-wise multiplication of relative depth maps with the scale factor. As a result, the unsupervised monocular depth estimation technology is extended from relative depth estimation in semi-structured scenes to absolute depth estimation in unstructured scenes. Experiments on the publicly available Mid-Air dataset and customized data demonstrate the effectiveness of our method in different cases and settings, as well as its robustness to navigation sensor noise. The proposed method only requires UAVs to be equipped with monocular camera and common navigation sensors, and the obtained absolute depth information can be directly used for downstream tasks, which is significant for this kind of vehicle that has rarely been explored in previous depth estimation studies.

Biodegradation of various grades of polyethylene microplastics by Tenebrio molitor and Tenebrio obscurus larvae: Effects on their physiology.

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 µm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae-1⋅day-1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics.

[Diagnostic values of anti-salivary gland protein-1 antibody combined with anti-parotid secretory protein antibody for Sjögren's syndrome].

OBJECTIVE: To assess the diagnostic value of anti-salivary gland protein-1 (SP1) antibody combined with anti-parotid secretory protein (PSP) antibody for Sjögren's syndrome (SS). METHODS: A total of 60 patients with primary SS (pSS) who were treated in the outpatient and inpatient department of Department of Rheumatology and Immunology of the Second Hospital of Hebei Medical University from January 2020 to December 2022 were collected. Thirty patients with other autoimmune diseases accompanied by dry mouth and/or dry eyes were collected as disease control group. Thirty healthy subjects from the physical examination center were collected for healthy control group, serum samples were obtained from all of them. Their general features and clinical information including clinical manifestations, laboratory examinations and other examinations were recorded. The 2016 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification criteria were adopted as the diagnostic standard of pSS. Immunoglobulin G (IgG) subtype of anti-SP1 antibody and anti-PSP antibody were detected by chemiluminescence immunoassay. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of anti-SP1 antibody and anti-PSP antibody in diagnosing pSS.The cli-nical characteristics of anti-SP1 antibody and anti-PSP antibody positive patients and negative patients in pSS group were further compared. Independent samples t test, Mann-Whitney U test, variance analysis, Kruskal-Wallis test, Chi-square test or Fisher's exact test and Spearman correlation analysis were used for statistical analysis. RESULTS: There was no significant difference in age (F=1.406, P=0.495) and gender (χ2=2.105, P=0.349) among pSS group, disease control group and healthy control group. The expression levels of anti-SP1 antibody (H=16.73, P < 0.001) and anti-PSP antibody (H=26.09, P < 0.001) were statistically different among the three groups. An intergroup comparison of anti-SP1 antibody expression levels showed that there was a statistically significant difference between pSS and healthy control group (P < 0.001), but no statistically significant difference between the other groups. Comparison of anti-PSP antibody expression levels between the groups showed that there were statistically significant differences between pSS and healthy control group (P < 0.001), and between disease control group and healthy control group (P=0.009), while no statistically significant differences between the other groups. The positive rate of anti-SP1 antibody in pSS group was significantly higher than that in disease control group and healthy control group (58.33% vs. 40.00% vs. 13.33%, P < 0.001). The positive rate of anti-PSP antibody in pSS group was significantly higher than that in disease control group and healthy control group (75.00% vs. 56.17% vs. 16.67%, P < 0.001). The area under the curve for anti-SP1 antibody was 0.688 (P < 0.001). The sensitivity and specificity of anti-SP1 antibody were 58.33% (35/60) and 70.00% (42/60) respectively, the positive predictive value was 66.04% (35/53) and the negative predictive value was 54.55% (42/77) of anti-SP1 antibody.The area under the curve of anti-PSP antibody was 0.720 (P < 0.001), with a sensitivity was 75.00% (45/60), and specificity was 63.33% (38/60).The positive predictive value and negative predictive value of anti-PSP antibody were 67.16% (45/67) and 71.70% (38/53) respectively. All the 13 pSS patients were negative for anti-Sjögren's syndrome A (SSA, including SSA52 and SSA60) antibody and anti- Sjögren's syndrome B (SSB) antibody. Among them, 11 patients were positive for both anti-SP1 antibody and anti-PSP antibody, 1 patient was positive for anti-SP1 antibody and 1 patient was positive for anti-PSP antibody. The clinical features of anti-SP1 antibody and anti-PSP antibody positive and negative groups were compared in pSS patients. The duration of disease in anti-SP1 antibody positive group was shorter (Z=-2.277, P=0.023) when compared with the negative patients. The patients with positive anti-PSP antibody were younger than those in the negative group (t=2.598, P < 0.05), the positive rate of rheumatoid factor (P=0.002) and the serum level of IgG (t=3.806, P=0.003) in anti-PSP antibody positive group were higher than in the negative group. Analysis of the correlation between anti-SP1 antibody and anti-PSP antibody in the pSS patients showed that there was significant correlation between them (r=0.801, P < 0.001). CONCLUSION: Both anti-SP1 antibody and anti-PSP antibody are valuable in the diagnosis of SS, and anti-SP1 antibody is helpful for the early diagnosis of pSS. The combined detection of anti-SP1 antibody and anti-PSP antibody is helpful for the early diagnosis of pSS patients with negative anti-SSA antibody and anti-SSB antibody.

The protease SENP2 controls hepatic gluconeogenesis by regulating the SUMOylation of the fuel sensor AMPKα.

Uncontrolled gluconeogenesis results in elevated hepatic glucose production in type 2 diabetes (T2D). The small ubiquitin-related modifier (SUMO)-specific protease 2 (SENP2) is known to catalyze deSUMOylation of target proteins, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic gluconeogenesis and the occurrence of T2D remain unknown. Herein, we established SENP2 hepatic knockout mice and found that SENP2 deficiency could protect against high-fat diet-induced hyperglycemia. Pyruvate- or glucagon-induced elevation in blood glucose was attenuated by disruption of SENP2 expression, whereas overexpression of SENP2 in the liver facilitated high-fat diet-induced hyperglycemia. Using an in vitro assay, we showed that SENP2 regulated hepatic glucose production. Mechanistically, the effects of SENP2 on gluconeogenesis were found to be mediated by the cellular fuel sensor kinase, 5'-AMP-activated protein kinase alpha (AMPKα), which is a negative regulator of gluconeogenesis. SENP2 interacted with and deSUMOylated AMPKα, thereby promoting its ubiquitination and reducing its protein stability. Inhibition of AMPKα kinase activity dramatically reversed impaired hepatic gluconeogenesis and reduced blood glucose levels in SENP2-deficient mice. Our study highlights the novel role of hepatic SENP2 in regulating gluconeogenesis and furthers our understanding of the pathogenesis of T2D.

Gap design to enable functionalities into nested antiresonant nodeless fiber based systems.

By modifying the interconnection design between standard single-mode fiber (SSMF) and nested antiresonant nodeless type hollow-core fiber (NANF), we create an air gap between SSMF and NANF. This air gap enables the insertion of optical elements, thus providing additional functions. We show low-loss coupling using various graded-index multimode fibers acting as mode-field adapters resulting in different air-gap distances. Finally, we test the gap functionality by inserting a thin glass sheet in the air gap, which forms a Fabry-Perot interferometer and works as a filter with an overall insertion loss of only 0.31 dB.

Hollow-core fiber with stable propagation delay between -150°C and +60°C.

Optical fibers with a low thermal coefficient of delay (TCD) have been developed for frequency and timing transmission/distribution. However, their temperature sensitivity changes as a function of temperature and, to date, no study of such fibers has demonstrated improved performance over extended temperature ranges, especially at sub-zero temperatures. Here, we show that a hollow core fiber (HCF) with a thin acrylate coating can have a TCD within ±2.0 ps/km/°C over a broad temperature range from -150°C to +60°C. In addition, this thinly coated HCF can be fully insensitive to temperature around -134°C, making it of interest, e.g., for laser stabilization close to cryogenic temperatures.

Hollow core fiber Fabry-Perot interferometers with reduced sensitivity to temperature: erratum.

In the original publication of our research article "Hollow core fiber Fabry-Perot interferometers with reduced sensitivity to temperature" [Opt. Lett.47, 2510 (2022)10.1364/OL.456589OPLEDP0146-9592], we identified an error that requires correction. The authors sincerely apologize for any confusion that may have arisen from this error. The correction does not affect the overall conclusions of the paper.