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Beige adipose tissue protects against obesity and related metabolic diseases by catabolizing stored energy to generate heat. While iron is essential for this process due to its role in mitochondrial function, the specific signaling mechanisms involved remain unclear. Here, we report that diet-induced obese mice exhibit a local iron deficiency in subcutaneous adipose tissue. Crucially, through integrated multi-omics approaches (RNA-seq and ATAC-seq), we identify that iron downregulates Paraspeckle component 1(PSPC1), which interacts with SMAD family member 3 (SMAD3) to promote its phosphorylation. The iron-induced reduction of PSPC1 alleviates the repressive signaling of SMAD3 on thermogenic gene expression, thereby inducing the beiging of white adipocytes. Furthermore, overexpression of Pspc1 in subcutaneous adipose tissue counteracted the iron-induced suppression of SMAD3 phosphorylation, effectively reversing iron-induced beiging of white adipocytes and its associated metabolic benefits. Collectively, our findings demonstrate that iron promotes the beiging of white adipocytes within subcutaneous adipose tissue and exerts anti-obesity effect by inhibiting PSPC1-SMAD3 axis, which may provide a potential therapeutic target for obesity and its related metabolic diseases. Graphical Abstract Iron protects against diet-induced obesity by promoting the beiging of adipocytes in white adipose tissue. This study identifies a novel regulatory mechanism where iron downregulates the expression of PSPC1. The reduction in PSPC1, which interacts with SMAD3, leads to decreased SMAD3 phosphorylation, thereby relieving its inhibition on thermogenic genes.

In order to investigate efficacy of FGF21 combine dexamethasone (Dex) on rheumatoid arthritis (RA) meanwhile reduce side effects of dexamethasone. We used combination therapy (Dex 15 mg/kg + FGF21 0.25 mg/kg, Dex 15 mg/kg + FGF21 0.5 mg/kg or Dex 15 mg/kg + FGF21 1 mg/kg) and monotherapy (Dex 15 mg/kg or FGF21 1 mg/kg) to treat CIA mice induced by chicken type II collagen, respectively. The effects of treatment were determined by arthritis severity score, histological damage, and cytokine production. The levels of oxidative stress parameters, liver functions, and other blood biochemical indexes were detected to determine FGF21鈥檚 efficiency to side effects of dexamethasone. Oil red O was performed to detect the effects of FGF21 and dexamethasone on fat accumulation in HepG2 cells. The mechanism of FGF21 improves the side effects of dexamethasone which was analyzed by Western blotting. This combination proved to be therapeutically more effective than dexamethasone or FGF21 used singly. FGF21 regulates oxidative stress and lipid metabolism by upregulating dexamethasone-inhibited SIRT-1 and then activating downstream Nrf-2/HO-1and PGC-1. FGF21 and dexamethasone are highly effective in the treatment of arthritis; meanwhile, FGF21 may overcome the limited therapeutic response and Cushing鈥檚 syndrome associated with dexamethasone.

Aim at the need of excessive freedom jointing robot real time measuring joint angle positions during work process, The engineer is an measure system of excessive freedom jointing robot, which are base on absoluteness type photo-electricity coder and TMS320F2812. The system have more group sixteen bits IO and SCI communicate interface, which can make jointing robot real time measuring, and implement the visual interface of the upper machine .The system has well real time and friendly human-machine interface, which is the same with minutely machining appliance extensive.

This study aimed to assess the impact of combined moxibustion therapy and Gua sha on enhancing functional independence, reducing fall risk, and alleviating pain in patients undergoing post-rehabilitation for multiple cerebral infarctions. In a prospective clinical trial, 67 patients diagnosed with multiple cerebral infarctions (age range: 40 to 93 years) were enrolled. Baseline health characteristics included a median hospital stay of 10 days, prevalent medical conditions such as hypertension (64.18%), and various comorbidities like spondylosis (17.91%) and heart disease (14.93%). Patients received moxibustion treatment daily for 20-30 minutes on specific acupoints of the upper and lower extremities. Additionally, Gua sha therapy targeting the the head, back, chest, abdomen, and selected acupoints was administered twice a week with an interval of 3 to 4 days. Assessments included Barthel Index (BI) for functional independence, Morse Fall Scale (MFS) for fall risk, and Visual Analogue Scale (VAS) for pain intensity before and after the intervention. After one week of rehabilitation, significant improvements were observed in the patient's functional independence, as indicated by a median BI score of 100 (IQR: 95-100), compared to the pre-rehabilitation median score of 95 (IQR: 90-100). The MFS score also showed a significant decrease after rehabilitation, with a median score of 35 (IQR: 35-45) compared to the pre-rehabilitation median score of 45 (IQR: 35-45). Additionally, pain intensity significantly decreased, with a median VAS score of 0 (range: 0-2) after rehabilitation, compared to the pre-rehabilitation median score of 0 (range: 0-3). Combined moxibustion therapy and Gua sha demonstrated positive effects on functional independence, fall risk reduction, and pain alleviation in post-rehabilitation for multiple cerebral infarctions. These findings suggest the potential of moxibustion and Gua sha as complementary interventions in stroke rehabilitation. The observed improvements in functional independence, fall risk, and pain underscore the potential benefits of these therapies for patients with multiple cerebral infarctions. Further exploration could delve into long-term effects, larger-scale trials, and mechanistic studies to elucidate the underlying pathways of efficacy.

The strength curves of lightweight aggregate concrete （LWAC） were tested based on detecting LWAC with density of 1 400-1 900 kg/m3 and LWAC with strength grade of LC15-LC50 by rebound method and ultrasonic-rebound combined method.The results show that the common measured strength curves tested by above two methods can not satisfy the required accuracy of LWAC strength test.In addition,specified compressive strength curves of testing LWAC by rebound method and ultrasonic-rebound combined method are obtained,respectively.

BACKGROUND:Hypothermia is associated with poor outcome in trauma patients;however,hemorrhagic shock（HS）model with anesthetized swine was different from that of clinical reality.To identify the effects of environmental hypothermia on HS,we investigated hemodynamics and oxygen dynamics in an unanesthetized swine model of HS under simulating hypothermia environment.METHODS:Totally 16 Bama pigs were randomly divided into ambient temperature group（group A）and low temperature group（group B）,8 pigs in each group.Venous blood（30 mL/kg）was continuously withdrawn for more than 15 minutes in conscious swine to establish a hemorrhagic shock model.Pulmonary arterial temperature（Tp）,heart rate（HR）,mean arterial pressure（MAP）,pulmonary arterial pressure（PAP）,pulmonary arterial wedge pressure（PAWP）,central venous pressure（CVP）,cardiac output（CO）,hemoglobin（Hb）,saturation of mixed venous blood（SvO2）and blood gas analysis were recorded at the baseline and different hemorrhagic shock time（HST）.The whole body oxygen delivery indices,DO2l and VO2l,and the O2 extraction ratio（O2ER）were calculated.RESULTS:Core body temperature in group A decreased slightly after the hemorrhagic shock model was established,and environmental hypothermia decreased in core body temperature.The mortality rate was significantly higher in group B（50%）than in group A（0%）.DO2l and VO2l decreased significantly after hemorrhage.No difference was found in hemodynamics,DO2l and VO2l between group A and group B,but the difference in pH,lactic acid and O2ER was significant between the two groups.CONCLUSION:Environmental hypothermia aggravated the disorder of oxygen metabolism after hemorrhagic shock,which was associated with poor prognosis.

Background：The diagnosis of myelodysplastic syndrome （MDS）,especially hypoplastic MDS,and MDS with low blast counts or normal karyotype may be problematic.This study characterized ID4 gene methylation in patients with MDS and aplastic anemia （AA）.Methods：The methylation status ofID4 was analyzed by bisulfite sequencing polymerase chain reaction （PCR） and quantitative real-time methylation-specific PCR （MethyLight PCR） in 100 patients with MDS and 31 patients with AA.Results：The MDS group had a higher ID4 gene methylation positivity rate （22.22%） and higher methylation levels （0.21 [0-3.79]） than the AA group （P 〈 0.05）.Furthermore,there were significant differences between the hypoplastic MDS and AA groups,the MDS with low blast count and the AA groups,and the MDS with normal karyotype and the AA groups.The combination of genetic and epigenetic markers was used in much more patients with MDS （62.5% [35/56]） than the use of genetic markers only （51.79% [29/56]）.Conclusions：These results showed that the detection ofID4 methylation positivity rates and levels could be a useful biomarker for MDS diagnosis.

Breast‐conserving surgery (BCS) is the predominant treatment approach for initial breast cancer. However, due to a lack of effective methods evaluating BCS margins, local recurrence caused by positive margins remains an issue. Accordingly, radiation therapy (RT) is a common modality in patients with advanced breast cancer. However, while RT also protects normal tissue and enhances tumor bed doses to improve therapeutic effects, current radiosensitizers cannot meet these urgent clinical needs. To address this, a novel self‐assembled multifunctional nanoprobe (NP) gadolinium (Gd)–diethylenetriaminepentaacetic acid–human serum albumin (HSA)@indocyanine green–Bevacizumab (NPs‐Bev) is synthesized to improve the efficacy of fluorescence‐image‐guided BCS and RT. Fluorescence image guidance of the second near infrared NP improves complete resection in tumor‐bearing mice and accurately discriminates between benign and malignant mammary tissue in transgenic mice. Moreover, targeting tumors with NPs induces more reactive oxygen species under X‐ray radiation therapy, which not only increases RT sensitivity, but also reduces tumor progression in mice. Interestingly, self‐assembled NPs‐Bev using HSA, the magnetic resonance contrast agent and Bevacizumab‐targeting vascular growth factor A, which are clinically safe reagents, are safe in vitro and in vivo. Therefore, the novel self‐assembled NPs provide a solid precision therapy platform to treat breast cancer. This study synthesizes a novel self‐assembled multifunctional nanoprobe (NP) gadolinium–diethylenetriaminepentaacetic acid–human serum albumin@indocyanine green (ICG)–Bevacizumab to successfully improve the efficacy of fluorescence‐image‐guided surgery and radiotherapy for breast cancer (BC). Interestingly, the platform's components are all clinically safe reagents. In the future, this NP is expected to provide a precision treatment platform for BC.

Notch receptors (Notch1–4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

The inflammatory response plays an important role in carcinogenesis. However, the functional role and mechanism of the UCHL3-associated inflammatory response in ovarian cancer remain to be characterized. Here, we report that increased expression of UCHL3 facilitates tumourigenesis by targeting TRAF2 protein, thereby enhancing the inflammatory response. The expression of UCHL3 is elevated in ovarian cancer patients and is associated with an unfavourable prognosis. Genetic ablation of UCHL3 was found to markedly block ovarian cancer cell proliferation, viability and migration both in vitro and in vivo. Mechanistically, luciferase pathway screening results show that NF-κB signalling is clearly activated compared with other pathways. UCHL3 was found to activate NF-κB signalling by deubiquitinating and stabilizing TRAF2, leading to tumourigenesis. Our results indicate that highly expressed UCHL3 enhances inflammation by stabilizing TRAF2, which in turn facilitates tumourigenesis in ovarian cancer, and that UCHL3 is a potential target for ovarian cancer patients with increased inflammation.