Phosphorylation of USP27X by PIM2 promotes glycolysis and breast cancer progression via deubiquitylation of MYC.

Aberrant cell proliferation is a hallmark of cancer, including breast cancer. Here, we show that USP27X is required for cell proliferation and tumorigenesis in breast cancer. We identify a PIM2-USP27X regulator of MYC signaling axis whose activity is an important contributor to the tumor biology of breast cancer. PIM2 phosphorylates USP27X, and promotes its deubiquitylation activity for MYC, which promotes its protein stability and leads to increase HK2-mediated aerobic glycolysis in breast cancer. Moreover, the PIM2-USP27X-MYC axis is also validated in PIM2-knockout mice. Taken together, these findings show a PIM2-USP27X-MYC signaling axis as a new potential target for breast cancer treatment.

Spatial distribution of lipophilic shellfish toxins in seawater and sediment in the Bohai Sea and the Yellow Sea, China.

Lipophilic shellfish toxins (LSTs) are widely distributed in marine environments worldwide, potentially threatening marine ecosystem health and aquaculture safety. In this study, two large-scale cruises were conducted in the Bohai Sea and the Yellow Sea, China, in spring and summer 2023 to clarify the composition, concentration, and spatial distribution of LSTs in the water columns and sediments. Results showed that okadaic acid (OA), dinophysistoxin-1 (DTX1) and/or pectenotoxin-2 (PTX2) were detected in 249 seawater samples collected in spring and summer. The concentrations of ∑LSTs in seawater were ranging of ND (not detected) -13.86, 1.60-17.03, 2.73-17.39, and 1.26-30.21 pmol L-1 in the spring surface, intermediate, bottom water columns and summer surface water layers, respectively. The detection rates of LSTs in spring and summer seawater samples were 97% and 100%, respectively. The high concentrations of ∑LSTs were mainly distributed in the north Yellow Sea and the northeast Bohai Sea in spring, and in the northeast Yellow Sea, the waters around Laizhou Bay and Rongcheng Bay in summer. Similarly, only OA, DTX1 and PTX2 were detected in the surface sediments. Overall, the concentration of ∑LSTs in the surface sediments of the northern Yellow Sea was higher than that in other regions. In sediment cores, PTX2 was mainly detected in the upper sediment samples, whereas OA and DTX1 were detected in deeper sediments, and LSTs can persist in the sediments for a long time. Overall, OA, DTX1 and PTX2 were widely distributed in the water column and surface sediments in the Bohai Sea and the Yellow Sea, China. The results of this study contribute to the understanding of spatial distribution of LSTs in seawater and sediment environmental media and provide basic information for health risk assessment of phycotoxins.

Regulation of opsin and circadian clock genes on mate-finding behavior of the day-flying red moth, Phauda flammans (Walker).

First, significantly higher mate-finding success was found under light condition than under constant darkness condition in Phauda flammans, a typical diurnal moth. We speculate that mate-finding behavior in P. flammans may be influenced by the light-sensitive opsin genes Long wavelength opsin (PfLW), Ultraviolet opsin (PfUV) and Blue opsin (PfBL), which are potentially regulated by both light-cues and endogenous circadian rhythms. Second, the circadian clock genes Period (PfPer), Timeless (PfTim), Cryptochrome1 (PfCry1), Cryptochrome2 (PfCRY2), Cryptochrome3 (PfCry-like), Clock (PfClk), Cycle (PfCyc), Vrille (PfVri), and Slimb (PfSli) were identified in P. flammans. Third, circadian rhythms in the relative expression levels of opsin and circadian clock genes were demonstrated via quantitative real-time PCR analysis, with peak expression coinciding with the mate-finding peak. Notably, the relative expression of PfLW in males P. flammans was significantly higher than that in females P. flammans at the mate-finding peaks Zeitgeber time (ZT) 8 and ZT 10 under light, while the expression of the opsin gene PfBL showed a similar pattern at ZT 10 under light. Additionally, the expression of the clock gene PfCry-like was significantly higher in males than in females at ZT 8 and ZT 10 under light, while PfPer, PfTim, PfClk and PfCyc exhibited similar male-biased expression patterns at ZT 10 under light. Conversely, PfCry1 and PfVri expression was significantly higher in females than in male at ZT 8 under light. In conclusion, sex differences were detected in the expression of opsin and circadian clock genes, which indicated that light-mediated regulation of these genes may contribute to the daytime mate-finding behavior of P. flammans.

Endoscopy for acute upper gastrointestinal bleeding: a protocol for systematic review and network meta-analysis of randomized controlled trials.

Background: Previous studies have reached mixed conclusions regarding the timing of endoscopic approaches for managing individuals with acute upper gastrointestinal bleeding (AUGIB). Therefore, the authors performed a protocol for systematic review and meta-analysis to assess the efficacy of various timing endoscopic approaches in managing individuals with AUGIB. Methods: The authors will search multiple databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Register. The search will cover the entire duration, starting from the establishment of these databases until July 2023. The selection criteria will focus on randomized controlled trials that assess the efficacy of endoscopy with varying timing in managing patients with AUGIB. The primary outcomes will include primary hemostasis and inpatient death. The secondary outcomes will include recurrent bleeding, need for surgical intervention, admission to the ICU, blood transfusion needs, and duration of hospitalization. Two reviewers will select the studies, extract data, and assess the risk of bias. A Bayesian approach will be used to conduct a network meta-analysis. Results: The results of this systematic review and meta-analysis will be published in peer-reviewed journals. Conclusion: This network meta-analysis provides comprehensive evidence of different timing endoscopic approaches for managing individuals with AUGIB.

Assessment of the disruption effects of tetrabromobisphenol A and its analogues on lipid metabolism using multiple in vitro models.

Tetrabromobisphenol A (TBBPA), a widely-used brominated flame retardant, has been revealed to exert endocrine disrupting effects and induce adipogenesis. Given the high structural similarities of TBBPA analogues and their increasing exposure risks, their effects on lipid metabolism are necessary to be explored. Herein, 9 representative TBBPA analogues were screened for their interference on 3T3-L1 preadipocyte adipogenesis, differentiation of C3H10T1/2 mesenchymal stem cells (MSCs) to brown adipocytes, and lipid accumulation of HepG2 cells. TBBPA bis(2-hydroxyethyl ether) (TBBPA-BHEE), TBBPA mono(2-hydroxyethyl ether) (TBBPA-MHEE), TBBPA bis(glycidyl ether) (TBBPA-BGE), and TBBPA mono(glycidyl ether) (TBBPA-MGE) were found to induce adipogenesis in 3T3-L1 preadipocytes to different extends, as evidenced by the upregulated intracellular lipid generation and expressions of adipogenesis-related biomarkers. TBBPA-BHEE exhibited a stronger obesogenic effect than did TBBPA. In contrast, the test chemicals had a weak impact on the differentiation process of C3H10T1/2 MSCs to brown adipocytes. As for hepatic lipid formation test, only TBBPA mono(allyl ether) (TBBPA-MAE) was found to significantly promote triglyceride (TG) accumulation in HepG2 cells, and the effective exposure concentration of the chemical under oleic acid (OA) co-exposure was lower than that without OA co-exposure. Collectively, TBBPA analogues may perturb lipid metabolism in multiple tissues, which varies with the test tissues. The findings highlight the potential health risks of this kind of emerging chemicals in inducing obesity, non-alcoholic fatty liver disease (NAFLD) and other lipid metabolism disorders, especially under the conditions in conjunction with high-fat diets.

Exogenous regulation of macronutrients promotes the accumulation of alkaloid yield in anisodus tanguticus (Maxim.) pascher.

BACKGROUND: Anisodus tanguticus (Maxim.) Pascher (A. tanguticus) is a valuable botanical for extracting tropane alkaloids, which are widely used in the pharmaceutical industry. Implementing appropriate cultivation methods can improve both the quality and yield of A. tanguticus. A two-year field experiment was conducted from 2021 to 2023 using a single-factor randomized complete block design replicated three times. The study examined the effects of different nutrient levels (nitrogen: 0, 75, 150, 225, 300, 375 kg/ha; phosphorus: 0, 600, 750, 900, 1050, 1200 kg/ha; potassium: 0, 75, 112.5, 150, 187.5, 225 kg/ha) on the growth, primary alkaloid contents, and alkaloid yield of A. tanguticus at different growth stages (S-Greening, S-Growing, S-Wilting; T-Greening, T-Growing, and T-Wilting) in both the roots and aboveground portions. RESULTS: Our results demonstrate that nutrient levels significantly affect the growth and alkaloid accumulation in A. tanguticus. High nitrogen levels (375 kg/ha) notably increased both root and aboveground biomass, while phosphorus had a minimal effect, especially on aboveground biomass. For alkaloid content (scopolamine, anisodamine, anisodine, atropine), a moderate nitrogen level (225 kg/ha) was most effective, followed by low potassium (75 kg/ha), with phosphorus showing a limited impact. Increased phosphorus levels led to a decrease in scopolamine content. During the T-Growing period, moderate nitrogen addition (225 kg/ha) yielded the highest alkaloid levels per unit area (205.79 kg/ha). In the T-Wilting period, low potassium (75 kg/ha) and low phosphorus (750 kg/ha) resulted in alkaloid levels of 146.91 kg/ha and 142.18 kg/ha, respectively. This indicates nitrogen has the most substantial effect on alkaloid accumulation, followed by potassium and phosphorus. The Douglas production function analysis suggests focusing on root biomass and the accumulation of scopolamine and atropine in roots to maximize alkaloid yield in A. tanguticus cultivation. CONCLUSIONS: Our findings show that the optimum harvesting period for A. tanguticus is the T-Wilting period, and that the optimal nitrogen addition is 225 kg/ha, the optimal potassium addition is 75 kg/ha, and the optimal phosphorus addition is 600 kg/ha or less.

[Spatio-temporal Evolution and Coordinated Development of Compactness with Carbon Emission Intensity in the Chengdu-Chongqing Urban Agglomeration].

Studies on the spatio-temporal variation and coordinated development level of compactness with carbon emission intensity in the Chengdu-Chongqing urban agglomeration is of great significance to achieve green, low-carbon, and high-quality development of society. The spatial-temporal differentiation, coupling coordination, and driving factors of the compactness and carbon emission intensity of the Chengdu-Chongqing urban agglomeration from 2010 to 2020 were analyzed by using the methods of comprehensive evaluation, carbon emission identical equality, coupling coordination, and the Geo-detector model. The results showed that:① The compactness of the Chengdu-Chongqing urban agglomeration continued to rise from 0.18 in 2010 to 0.22 in 2020, with an overall increase of 22.22 %, in which the contribution rate of economic compactness to urban compactness increased yearly. There were significant regional differences in the compactness of cities. The high-value areas were concentrated in Chengdu, Deyang, and Mianyang in the northwest and Zigong, Neijiang, and Luzhou in the southwest, whereas the low-value areas were distributed in the middle. Ya'an was always the area with the lowest compactness of urban agglomeration. ② The carbon emission intensity of the Chengdu-Chongqing urban agglomeration was decreasing yearly, with a decrease rate of 39.57 % during the study period. The carbon emission intensity in the southern part of the urban agglomeration was higher than that in other regions as a whole, whereas Chengdu and Chongqing were low-value areas all the year round, and the regional differences of carbon emission intensity were gradually narrowing. ③ The coupling degree between urban compactness and carbon emission intensity changed from the antagonistic stage to the running-in stage; the coupling coordination degree increased notably, from 0.21 in 2010 to 0.69 in 2020; and the two systems gradually moved towards benign and coordinated development. The coupling coordination between the northwest of the urban agglomeration (Chengdu, Deyang, and Mianyang) and the south of Sichuan (Zigong and Luzhou) was generally high. Industrial structure, scientific and technological innovation, urbanization level, government intervention, and environmental livability all had significant effects on the coupling and coordination of the two systems. ④ Optimizing industrial structure, strengthening scientific and technological support, improving the quality of urbanization development, implementing active policy guidance, and building green barriers were effective ways to promote the coordinated development of compactness and low carbon in the Chengdu-Chongqing urban agglomeration.

CFD-DEM method is used to study the multi-phase coupling slag discharge flow field of gas-lift reverse circulation in drilling shaft sinking.

To elucidate the distribution law of the multiphase coupling slag discharge flow field in gas-lift reverse circulation during drilling shaft sinking, a numerical analysis model of gas-liquid-solid multiphase coupling slag discharge was established by CFD-DEM (Coupling of computational fluid dynamics and discrete element method) method, taking the drilling of North Wind well in Taohutu Coal Mine as an example. This model presented the distribution of the multiphase flow field in the slag discharge pipe and at the bottom hole, and was validated through experimentation and theoretical analysis. Finally, the impact of factors, including bit rotation speed, gas injection rate, air duct submergence ratio, and mud viscosity on the slag discharge flow field was clarified. The results indicated that the migration of rock slag at the bottom of the well was characterized by "slip, convergence, suspension, adsorption, and lifting". The slag flow in the discharge pipe exhibited the states of "high density, low flow rate" and "low density, high flow rate", respectively. The multiphase fluid flow patterns in the well bottom and slag discharge pipe were horizontal and axial flows, respectively. The model test of the gas lift reversed circulation slag discharge and the theoretical model of the bottom hole fluid velocity distribution confirmed the accuracy of the multiphase coupling slag discharge flow field distribution model. The rotation speed of the drill bit had the most significant impact on the bottom hole flow field. Increasing the rotation speed of the drill bit can significantly enhance the tangential velocity of the bottom hole fluid, increase the pressure difference between the bottom hole and annular mud column, and improve the adsorption capacity of the slag suction port. These findings can provide valuable insights for gas lift reverse circulation well washing in western drilling shaft sinking.

A Bacillus velezensis strain isolated from oats with disease-preventing and growth-promoting properties.

Endophytes have been shown to promote plant growth and health. In the present study, a Bacillus velezensis CH1 (CH1) strain was isolated and identified from high-quality oats, which was capable of producing indole-3-acetic acid (IAA) and strong biofilms, and capabilities in the nitrogen-fixing and iron carriers. CH1 has a 3920 kb chromosome with 47.3% GC content and 3776 code genes. Compared genome analysis showed that the largest proportion of the COG database was metabolism-related (44.79%), and 1135 out of 1508 genes were associated with the function "biosynthesis, transport, and catabolism of secondary metabolites." Furthermore, thirteen gene clusters had been identified in CH1, which were responsible for the synthesis of fifteen secondary metabolites that exhibit antifungal and antibacterial properties. Additionally, the strain harbors genes involved in plant growth promotion, such as seven putative genes for IAA production, spermidine and polyamine synthase genes, along with multiple membrane-associated genes. The enrichment of these functions was strong evidence of the antimicrobial properties of strain CH1, which has the potential to be a biofertilizer for promoting oat growth and disease resistance.

Expanding the horizons of targeted protein degradation: A non-small molecule perspective.

Targeted protein degradation (TPD) represented by proteolysis targeting chimeras (PROTACs) marks a significant stride in drug discovery. A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation. Non-small-molecule-based approaches play an irreplaceable role in this field. A wide variety of agents spanning a broad chemical spectrum, including peptides, nucleic acids, antibodies, and even vaccines, which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms. Herein we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs, including three major trajectories, to provide insights for the design strategies based on novel paradigms.

Comparative Study of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy and the Loop Electrosurgical Excision Procedure for the Treatment of Cervical High-Grade Squamous Intraepithelial Lesions.

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24-51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL.

The Role of EEG microstates in predicting oxcarbazepine treatment outcomes in patients with newly-diagnosed focal epilepsy.

PURPOSE: Microstates represent the global and topographical distribution of electrical brain activity from scalp-recorded EEG. This study aims to explore EEG microstates of patients with focal epilepsy prior to medication, and employ extracted microstate metrics for predicting treatment outcomes with Oxcarbazepine monotherapy. METHODS: This study involved 25 newly-diagnosed focal epilepsy patients (13 females), aged 12 to 68, with various etiologies. Patients were categorized into Non-Seizure-Free (NSF) and Seizure-Free (SF) groups according to their first follow-up outcomes. From pre-medication EEGs, four representative microstates were identified by using clustering. The temporal parameters and transition probabilities of microstates were extracted and analyzed to discern group differences. With generating sample method, Support Vector Machine (SVM), Logistic Regression (LR), and Naïve Bayes (NB) classifiers were employed for predicting treatment outcomes. RESULTS: In the NSF group, Microstate 1 (MS1) exhibited a significantly higher duration (mean±std. = 0.092±0.008 vs. 0.085±0.008, p = 0.047), occurrence (mean±std. = 2.587±0.334 vs. 2.260±0.278, p = 0.014), and coverage (mean±std. = 0.240±0.046 vs. 0.194±0.040, p = 0.014) compared to the SF group. Additionally, the transition probabilities from Microstate 2 (MS2) and Microstate 3 (MS3) to MS1 were increased. In MS2, the NSF group displayed a stronger correlation (mean±std. = 0.618±0.025 vs. 0.571±0.034, p < 0.001) and a higher global explained variance (mean±std. = 0.083±0.035 vs. 0.055±0.023, p = 0.027) than the SF group. Conversely, Microstate 4 (MS4) in the SF group demonstrated significantly greater coverage (mean±std. = 0.388±0.074 vs. 0.334±0.052, p = 0.046) and more frequent transitions from MS2 to MS4, indicating a distinct pattern. Temporal parameters contribute major predictive role in predicting treatment outcomes of Oxcarbazepine, with area under curves (AUCs) of 0.95, 0.70, and 0.86, achieved by LR, NB and SVM, respectively. CONCLUSION: This study underscores the potential of EEG microstates as predictive biomarkers for Oxcarbazepine treatment responses in newly-diagnosed focal epilepsy patients.

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain.

Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Antibiotic-Induced Gut Microbiota Dysbiosis Modulates Host Transcriptome and m6A Epitranscriptome via Bile Acid Metabolism.

Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6-methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

Identification of Hydrocarbon Sulfonates as Previously Overlooked Transthyretin Ligands in the Environment.

Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased in recent years. However, known TDCs can only explain a small portion (∼1%) of in vitro human transthyretin (hTTR) binding activities in environmental samples, indicating the existence of unknown hTTR ligands. In this study, we aimed to identify the major environmental hTTR ligands by employing protein Affinity Purification with Nontargeted Analysis (APNA). hTTR binding activities were detected in all 11 indoor dust and 9 out of 10 sewage sludge samples by the FITC-T4 displacement assay. By using APNA, 31 putative hTTR ligands were detected including perfluorooctanesulfonate (PFOS). Two of the most abundant ligands were identified as hydrocarbon surfactants (e.g., dodecyl benzenesulfonate). Moreover, another abundant ligand was surprisingly identified as a disulfonate fluorescent brightener, 4,4'-bis(2-sulfostyryl)biphenyl sodium (CBS). CBS was validated as a nM-affinity hTTR ligand with an IC50 of 345 nM. In total, hydrocarbon surfactants and fluorescent brighteners explain 1.92-17.0 and 5.74-54.3% of hTTR binding activities in dust and sludge samples, respectively, whereas PFOS only contributed <0.0001%. Our study revealed for the first time that hydrocarbon sulfonates are previously overlooked hTTR ligands in the environment.

Huangqi Guizhi Wuwu Decoction suppresses inflammation and bone destruction in collagen-induced arthritis mice.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction (HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis (CIA) mouse model. Methods: DBA/1J female mice were used to establish the collagen-induced arthritis (CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay (ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors mRNA and protein levels after HGWD intervention in RAW 264.7 cells. Results: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints, reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function. HGWD decreased the expression of mRNA for inflammatory factors and the protein expression levels of p-NF-кB and IL-17. Conclusion: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.

The Time-Dependent Interfacial Adhesion between Artificial Rock and Fresh Mortar Modified by Nanoclay.

The time-dependent interfacial adhesion between rock and fresh mortar is key for printing concrete linings in mountain tunnels. However, a scientific deficit exists in the time-dependent evolution of the interfacial adhesion, which can cause adhesion failure when printing tunnel lining. Nanoclay has the potential to increase the interfacial adhesion and eliminate the adhesion failure. Before the actual printing of tunnel linings, the time-dependent interfacial adhesion between artificial rock and fresh mortar modified by nanoclay should be understood. This paper studied the time-dependent interfacial adhesion based on fast tack tests, fast shear tests, and isothermal calorimetry tests. With the addition of nanoclay, the maximum tensile stress and the maximum shear stress increased. Compared with a reference series, the maximum interfacial tensile stress in a 0.3% nanoclay series increased by 106% (resting time 1 min) and increased by 209% (resting time 32 min). A two-stage evolution of the interfacial adhesion was found with the addition of nanoclay. In the first stage, the time-dependent interfacial adhesion increased rapidly. A 0.3% NC series showed an increase rate six times higher than that of the reference series. As the matrices aged, the increase rate slowed down and followed a linear pattern of increase, still higher than that of the reference series. The stiffening of fresh matrices resulted in the interface failure mode transition from a ductile failure to a brittle failure. The effect of nanoclay on flocculation and on accelerating the hydration contributed to the time-dependent interfacial adhesion between artificial rock and fresh mortar.

The causal relationship between serum metabolites and acne vulgaris: a Mendelian randomization study.

In individuals with acne vulgaris, alterations occur in serum metabolite composition, yet the exact causal link between these metabolites and acne development remains elusive. Using genome-wide association datasets, we performed bidirectional Mendelian randomization (MR) to investigate the potential causal relationship between 309 serum metabolites and acne vulgaris. We performed sensitivity analysis to evaluate the presence of heterogeneity and pleiotropy. Forward MR analysis found 14 serum metabolites significantly associated with acne vulgaris, and reverse MR analysis found no significant association between acne vulgaris and these serum metabolites. Through validation using data from the FinnGen database of acne vulgaris studies, we found a conclusive and significant correlation between stearoylcarnitine and acne vulgaris. This provides new evidence in the search for new targets for the treatment of acne vulgaris.

The Application of "Table Tennis Racquet" Random Skin Flap in the Treatment of Facial Skin Carcinoma.

BACKGROUND: The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. METHODS: A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. RESULTS: All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. CONCLUSIONS: This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.

Reversible Switching Between Microwave Absorption and EMI Shielding of VO2 Composite Foam.

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.