Insights into copper(I) phenylacetylide with in-situ transformation of oxygen and enhanced visible-light response for water decontamination: Cu-O bond promotes exciton dissociation and charge transfer.

The widespread contamination of hexavalent chromium (Cr(VI)), pharmaceuticals and personal care products (PPCPs), and dyes is a growing concern. necessitating the development of convenient and effective technologies for their removal. Copper(I) phenylacetylide (PhC2Cu) has emerged as a promising photocatalyst for environmental remediation. In this study, we introduced a functional Cu-O bond into PhC2Cu (referred to as OrPhC2Cu) by creatively converting the adsorbed oxygen on the surface of PhC2Cu into a Cu-O bond to enhance the efficiency of Cr(VI) photoreduction, PPCPs photodegradation, and dyes photodegradation through a facile vacuum activating method. The incorporation of the Cu-O bond optimized the electron structure of OrPhC2Cu, facilitating exciton dissociation and charge transfer. The exciton dissociation behavior and charge transfer mechanism were systematically investigated for the first time in the OrPhC2Cu system by photoelectrochemical tests, fluorescence and phosphorescence (PH) techniques, and density functional theory (DFT) calculations. Remarkably, the enhanced visible-light response of OrPhC2Cu improved photon utilization and significantly promoted the generation of reactive species (RSs), leading to the highly efficient Cr(VI) photoreduction (98.52% within 25 min) and sulfamethazine photodegradation (94.65% within 60 min), with 3.91 and 5.23 times higher activity compared to PhC2Cu. Additionally, the photocatalytic efficiency of OrPhC2Cu in degrading anionic dyes surpassed that of cationic dyes. The performance of the OrPhC2Cu system in treating electroplating effluent or natural water bodies suggests its potential for practical applications.

Alteration of prefrontal cortex and its associations with emotional and cognitive dysfunctions in adolescent borderline personality disorder.

The neurobiological mechanism of borderline personality disorder (BPD) in adolescents remains unclear. The study aimed to assess the alterations in neural activity within prefrontal cortex in adolescents with BPD and investigate the relationship of prefrontal activity with emotional regulation and cognitive function. This study enrolled 50 adolescents aged 12-17 years with BPD and 21 gender and age-matched healthy control (HC) participants. Study assessment for each participant included a brain resting-state functional MRI (rs-fMRI), clinical assessment questionnaires such as Borderline Personality Features Scale (BPFS), Difficulties in Emotion Regulation Scale (DERS), Ottawa Self-Injury Inventory and Childhood Trauma Questionnaire (CTQ) and cognitive testing with Stroop Color-Word Test (SCWT). Fractional amplitude of low-frequency fluctuations (fALFF) and seed-based functional connectivity (FC) were obtained from rs-fMRI analysis. Correlation analysis was also performed to evaluate the associations of the neuroimaging metrics such as fALFF and FC with clinical assessment questionnaire and cognitive testing scores. Adolescents with BPD showed increased fALFF values in the right inferior frontal gyrus and decreased activity in the left middle frontal gyrus as compared to the HC group (p < 0.05, cluster size ≥ 100, FWE correction). In adolescents with BPD, increased fALFF in the right inferior frontal gyrus was related to the BPFS (emotional dysregulation), DERS-F (lacking of emotional regulation strategies) and Ottawa Self-Injury Inventory-4 C scores (internal emotional regulation function of self-injurious behavior). The reduced fALFF in the left middle frontal gyrus was associated with the SCWT-A (reading characters) and the SCWT-B (reading color) scores. Additionally, the fALFF values in the left middle frontal gyrus and the right inferior frontal gyrus were related to the CTQ-D (emotional neglect) (p < 0.05). The left middle frontal gyrus exhibited increased FC with the right hippocampus, left inferior temporal gyrus and right inferior frontal gyrus (voxel p < 0.001, cluster p < 0.05, FWE correction). The increased FC between the left middle frontal gyrus and the right hippocampus was related to the SCWT-C (cognitive flexibility) score. We observed diverging changes in intrinsic brain activity in prefrontal cortex, and neural compensatory changes to maintain function in adolescents with BPD. In addition, decreased neural function was closely associated with emotional dysregulation, while increased neural function as indicated by brain activity and FC was associated with cognitive dysfunction. These results indicated that alterations of intrinsic brain activity may be one of the underlying neurobiological markers for clinical symptoms in adolescents with BPD.

Sensitive Fluorescent Biosensor Reveals Differential Subcellular Regulation of PKC.

The protein kinase C (PKC) family of serine/threonine kinases, which consist of three distinctly regulated subfamilies, have long been established as critical for a variety of cellular functions. However, how PKC enzymes are regulated at different subcellular locations, particularly at emerging signaling hubs such as the ER, lysosome, and Par signaling complexes, is unclear. Here, we present a sensitive Excitation Ratiometric (ExRai) C Kinase Activity Reporter (ExRai-CKAR2) that enables the detection of minute changes in subcellular PKC activity. Using ExRai-CKAR2 in conjunction with an enhanced diacylglycerol (DAG) biosensor capable of detecting intracellular DAG dynamics, we uncover the differential regulation of PKC isoforms at distinct subcellular locations. We find that G-protein coupled receptor (GPCR) stimulation triggers sustained PKC activity at the ER and lysosomes, primarily mediated by Ca2+ sensitive conventional PKC (cPKC) and novel PKC (nPKC), respectively, with nPKC showing high basal activity due to elevated basal DAG levels on lysosome membranes. The high sensitivity of ExRai-CKAR2, targeted to either the cytosol or Par-complexes, further enabled us to detect previously inaccessible endogenous atypical PKC (aPKC) activity in 3D organoids. Taken together, ExRai-CKAR2 is a powerful tool for interrogating PKC regulation in response to physiological stimuli.

High pyroptosis activity in pancreatic adenocarcinoma: poor prognosis and oxaliplatin resistance.

BACKGROUND: Pyroptosis, as a type of inflammatory programmed cell death, has been studied in inflammatory diseases and numerous cancers but its role in pancreatic ductal adenocarcinoma (PDAC) remains further exploration. METHODS: A TCGA-PDAC cohort was enrolled for bioinformatics analysis to investigate the effect of pyroptosis on the prognosis and drug sensitivity of patients. PA-TU-8988T and CFPAC-1 cells were selected for investigating the role of GSDMC in PDAC. RESULTS: A distinct classification pattern of PDAC mediated by 21 pyroptosis-related genes (PRGs) was identified. It was suggested that higher pyroptosis activity was associated with poor prognosis of patients and higher tumor proliferation rates. We further established a prognostic model based on three PRGs (GSDMC, CASP4 and NLRP1) and the TCGA-PDAC cohort was classified into low and high-risk subgroups. It is noteworthy that the high-risk group showed significantly higher tumor proliferation rates and was proved to be highly correlated with oxaliplatin resistance. Further experiments suggested that overexpression of GSDMC promoted the proliferation and oxaliplatin resistance of PA-TU-8988T cells in vitro and vivo, while downregulation of GSDMC showed opposite effects in CFPAC-1 cells. Finally, we found that the activation of pentose phosphate pathway (PPP) was the mechanism by which GSDMC overexpression promoted the proliferation and oxaliplatin resistance of pancreatic cancer cells. CONCLUSIONS: In this study, we found that higher pyroptosis activity is associated with worse prognosis and oxaliplatin resistance of PDAC patients. In addition, as a core effector of pyroptosis, GSDMC promoted proliferation and oxaliplatin resistance of pancreatic cancer cells, which will provide new therapeutic target for PDAC patients.

Endosome positioning coordinates spatially selective GPCR signaling.

G-protein-coupled receptors (GPCRs) can initiate unique functional responses depending on the subcellular site of activation. Efforts to uncover the mechanistic basis of compartmentalized GPCR signaling have concentrated on the biochemical aspect of this regulation. Here we assess the biophysical positioning of receptor-containing endosomes as an alternative salient mechanism. We devise a strategy to rapidly and selectively redistribute receptor-containing endosomes 'on command' in intact cells without perturbing their biochemical composition. Next, we present two complementary optical readouts that enable robust measurements of bulk- and gene-specific GPCR/cyclic AMP (cAMP)-dependent transcriptional signaling with single-cell resolution. With these, we establish that disruption of native endosome positioning inhibits the initiation of the endosome-dependent transcriptional responses. Finally, we demonstrate a prominent mechanistic role of PDE-mediated cAMP hydrolysis and local protein kinase A activity in this process. Our study, therefore, illuminates a new mechanism regulating GPCR function by identifying endosome positioning as the principal mediator of spatially selective receptor signaling.

Clinical Study on the Thoracodorsal Artery Perforator Flap in Breast-Conserving Reconstruction of T2 Breast Cancer.

BACKGROUND: Breast-conserving surgery combined with oncoplastic breast surgery has become the standard surgical treatment for early breast cancer. OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of the thoracodorsal artery perforator flap (TDAPF) in breast-conserving reconstruction of T2 breast cancer. METHODS: Thirty patients with T2 breast cancer admitted to our hospital from January 2019 to December 2020 were enrolled to receive pedicled TDAPF for repairing breast defects after breast-conserving surgery. Intraoperative conditions, postoperative complications, and shape satisfaction after breast reconstruction were recorded. RESULTS: The operation was successfully completed in all 30 patients, with an operation time of 177.77 ± 24.39 min, bleeding of 44.17 ± 7.67 mL, and length of hospital stay of 5.23 ± .97 d. There was no deformity or seroma at the donor site. Breast shape recovered well after operation. After operation, one patient had fat liquefaction in the recipient site, which healed well after wound treatment. The incidence of postoperative complications was 3.33%. Postoperative follow-up lasted 16-28 months, with a median of 22 months. The Breast-Q score for breast satisfaction was 61.83 ± 12.87 at 6 months after operation, compared to 62.07 ± 11.78 before operation (P > .05). CONCLUSIONS: TDAPF, featuring a high survival rate, moderate flap area, fewer postoperative complications, and high satisfaction with breast shape after operation. For east asian women with moderate breast size, TDAPF is a safe, effective choice for repairing defects in breast-conserving surgery for T2 breast cancer.

m6A eraser FTO impairs gemcitabine resistance in pancreatic cancer through influencing NEDD4 mRNA stability by regulating the PTEN/PI3K/AKT pathway.

BACKGROUND: Gemcitabine resistance has brought great challenges to the treatment of pancreatic cancer. The N6-methyladenosine (m6A) mutation has been shown to have a significant regulatory role in chemosensitivity; however, it is not apparent whether gemcitabine resistance can be regulated by fat mass and obesity-associated protein (FTO). METHODS: Cells with established gemcitabine resistance and tissues from pancreatic cancer patients were used to evaluate FTO expression. The biological mechanisms of the effects of FTO on gemcitabine resistant cells were investigated using CCK-8, colony formation assay, flow cytometry, and inhibitory concentration 50. Immunoprecipitation/mass spectrometry, MeRIP-seq, RNA sequencing and RIP assays, RNA stability, luciferase reporter, and RNA pull down assays were employed to examine the mechanism of FTO affecting gemcitabine resistant pancreatic cancer cells. RESULTS: The results revealed that FTO was substantially expressed in cells and tissues that were resistant to gemcitabine. Functionally, the gemcitabine resistance of pancreatic cancer could be enhanced by FTO, while its depletion inhibited the growth of gemcitabine resistant tumor cells in vivo. Immunoprecipitation/mass spectrometry showed that the FTO protein can be bound to USP7 and deubiquitinated by USP7, leading to the upregulation of FTO. At the same time, FTO knockdown significantly decreased the expression level of NEDD4 in an m6A-dependent manner. RNA pull down and RNA immunoprecipitation verified YTHDF2 as the reader of NEDD4, which promoted the chemoresistance of gemcitabine resistant cells. FTO knockdown markedly increased the PTEN expression level in an NEDD4-dependent manner and influenced the chemosensitivity to gemcitabine through the PI3K/AKT pathway in pancreatic cancer cells. CONCLUSION: In conclusion, we found that gemcitabine resistance in pancreatic cancer can be influenced by FTO that demethylates NEDD4 RNA in a m6A-dependent manner, which then influences the PTEN expression level and thereby affects the PI3K/AKT pathway. We also identified that the FTO level can be upregulated by USP7.

Carbon nitride nanotubes anchored with Cu(I) triggers peracetic acid activation with visible light for removal of antibiotic contaminants: Probing mechanisms of non-radical pathways and identifying active sites.

The peracetic acid (PAA)-activation process has attracted much attention in wastewater treatment. However, the low electron efficiency at the interface between heterogeneous catalysts and PAA has affected its practical application. For this study, we developed a carbon nitride hollow-nanotube catalysts with dispersed Cu(I) sites (Cu(I)-TCN) for the photocatalytic activation of PAA for antibiotics degradation. The obtained Cu(I)-TCN catalyst demonstrated an enhanced capacity for visible light harvesting along with increased charge transfer rates. Specifically, the developed Cu(I)-TCN/visible light/PAA system was able to completely remove antibiotics within 20 min, with a kinetic constant that was 25 times higher than a Cu(I)-TCN/visible light system, and 83 times higher than Cu(I)-TCN/PAA systems. Scavenging experiment and electron paramagnetic resonance (EPR) indicated that singlet oxygen was dominant reactive specie for sulfisoxazole (SIZ) removal. Besides, electrochemical tests and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy verified that the electron transfer efficiency of PAA activation was promoted due to the formation of inner-sphere interactions between PAA and Cu(I)-TCN, resulting in the quick removal of antibiotics. Further, after exposure to visible light, the Cu(I)-TCN excited photogenerated electrons which supplemented the electrons consumed in the reaction and drove the valence cycle of Cu ions. Overall, this research offered novel insights into the non-radical pathway for heterogeneous visible light-driven advanced oxidation processes and their potential for practical wastewater remediation.

Strategy for improvement of molecular oxygen activation capacity of PPECu by chlorine doping for water decontamination.

The activation of molecular oxygen and generation of reactive oxygen species (ROS) play important roles in the efficient removal of contaminants from aqueous ecosystems. Herein, using a simple and rapid solvothermal process, we developed a chlorine-doped phenylethynylcopper (Cl/PPECu) photocatalyst and applied it to visible light degradation of sulfamethazine (SMT) in aqueous media. The Cl/PPECu was optimized to have a 2.52 times higher steady-state concentration of O2•- (3.62 × 10-5 M) and a 28.87 times higher degradation rate constant (0.2252 min-1) for SMT compared to pure PPECu. Further, the effectiveness of Cl/PPECu in treating sulfonamide antibiotics (SAs) in real water systems was verified through an investigation involving natural water bodies, SAs, and ambient sunlight. The energy band structure, DFT calculation and correlation heat map indicated that the addition of chlorine modulated the local electronic structure of PPECu, leading to an improvement in the electron-hole separation, enhanced the O2 activation, and promoted the generation of ROSs. This study not only puts forward innovative ideas for the eco-compatible remediation of environmental pollution using PPECu, but also sheds new light on the activation of oxygen through elemental doping.

Simplified synthesis of direct Z-scheme Bi2WO6/PhC2Cu heterojunction that shows enhanced photocatalytic degradation of 2,4,6-TCP: Kinetic study and mechanistic insights.

For this work, we employed n-type Bi2WO6 and p-type PhC2Cu to formulate a direct Z-scheme Bi2WO6/PhC2Cu (PCBW) photocatalyst via simplified ultrasonic stirring technique. An optimal 0.6PCBW composite exhibited the capacity to rapidly photodegrade 2,4,6-TCP (98.6% in 120 min) under low-power blue LED light, which was 8.53 times and 12.53 times faster than for pristine PhC2Cu and Bi2WO6, respectively. Moreover, electron spin resonance (ESR), time-resolved PL spectra, and quantitative ROS tests indicated that the PCBW enhanced the separation capacity of photocarriers. It also more readily associated with dissolved oxygen in water to generate reactive oxygen species (ROS). Among them, the ability of PCBW to produce ·O2- in one hour was 12.07 times faster than for pure PhC2Cu. In addition, the H2O2 formation rate and apparent quantum efficiency of PCBW are 10.73 times that of PhC2Cu, which indicates that PCBW not only has excellent photocatalytic performance, but also has outstanding ROS production ability. Furthermore, Ag photodeposition, in situ X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations were utilized to determine the photogenerated electron migration paths in the PCBW, which systematically confirmed that Z-scheme heterojunction were successfully formed. Finally, based on the intermediate products, three potential 2,4,6-TCP degradation pathways were proposed.

Key role of Fe(VI)-activated Bi2WO6 in the photocatalytic oxidation of sulfonamides: Mediated electron transfer mechanism.

The widespread use of sulfonamides (SAs) in animals and human infections has raised significant concerns regarding their presence in ambient waterways and potential for inducing antimicrobial resistance. Herein, we report on the capacity of ferrate (VI) (FeVIO42-, Fe(VI)) to facilitate the photocatalytic degradation of sulfamethazine (SMT) via bismuth tungstate (Bi2WO6, BWO) under blue LED light (Vis/BWO/Fe(VI)) exposure, at rates that were 45-fold faster than BWO photocatalysis. Both the stepwise and time-series addition of Fe(VI) contributed to the degradation. Multiple lines of evidence confirmed that the common reactive species (RSs) in BWO-based photocatalytic systems and Fe(VI)-involved systems (e.g., •OH/h+, O2•-, 1O2 and Fe(V)/Fe(IV)) played subtle roles in our study system. Herein, for the first time, it was discovered that the precursor complex (BWO-Fe(V)/Fe(IV)* )) was the main contributor to induce electron transfer of SAs through the "conductive bridge" effect of BWO. The studied system was able to effectively degrade SMT in synthetic hydrolyzed urine (SHU) with low interference from background substances in water. This work not only offers a novel facilitation strategy for BWO, but also holds a great application prospect for contamination remediation in urine.

Midterm follow-up results of a novel technique: Contralateral breast overlapped reconstruction after mastectomy for unilateral breast cancer.

BACKGROUND: The breasts of Oriental women are characterized by an obvious scar constitution and a relatively small mammary gland volume. Thus, plastic surgery, which is now popular in the West, is not suitable for most patients in China, and Chinese surgeons are searching for symmetrical plastic surgery options that are suitable for patients with breast tumors, unilateral breast implants and an obvious scar constitution. METHODS: Between January 2016 and December 2019, 15 patients underwent contralateral breast overlapped reconstruction (COBOR) at the Affiliated Hospital of Putian University. We assessed their clinicopathological data, complications, cosmetic satisfaction and quality of life. RESULTS: The mean age was 41.6 years (range, 31-54 years), the average BMI was 24.36 kg/m2 (range, 20.3-28.4 kg/m2), the most common tumor location was the upper outer quadrant (n = 9), the mean preoperative tumor size was 21.11 mm (range, 7-42 mm), and 4 patients underwent neoadjuvant chemotherapy. The cancer grades and histological types were as follows: G3 nonspecial type (NST), 3 cases; G2 NST, 6 cases; G2 lobular carcinoma, 1 case; and ductal carcinoma in situ (DCIS), 5 cases. The nipple margin was negative in all of these cases. Among them, there was 1 case of poor wound healing caused by subcutaneous fat liquefaction around the incision. In another case, partial nipple necrosis occurred on the affected side due to an insufficient nipple blood supply after the operation and healed after debridement and dressing changes. There were no cases of tumor recurrence during the mean follow-up of 22.53 months (range, 11-47 months). The BREAST-Q scores showed that COBOR provided good patient satisfaction. CONCLUSION: For Oriental patients with small breasts, COBOR, which results in fewer scars, good symmetry and good satisfaction, is an effective and safe surgical method. However, larger studies with longer follow-up periods are needed to obtain more reliable postoperative results.

Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter.

AMP-activated protein kinase (AMPK) is a master regulator of cellular energetics which coordinates metabolism by phosphorylating a plethora of substrates throughout the cell. But how AMPK activity is regulated at different subcellular locations for precise spatiotemporal control over metabolism is unclear. Here we present a sensitive, single-fluorophore AMPK activity reporter (ExRai AMPKAR), which reveals distinct kinetic profiles of AMPK activity at the mitochondria, lysosome, and cytoplasm. Genetic deletion of the canonical upstream kinase liver kinase B1 (LKB1) results in slower AMPK activity at lysosomes but does not affect the response amplitude at lysosomes or mitochondria, in sharp contrast to the necessity of LKB1 for maximal cytoplasmic AMPK activity. We further identify a mechanism for AMPK activity in the nucleus, which results from cytoplasmic to nuclear shuttling of AMPK. Thus, ExRai AMPKAR enables illumination of the complex subcellular regulation of AMPK signaling.

Interface behavior and removal mechanisms of human pathogenic viruses in anaerobic membrane bioreactor (AnMBR).

Effective removal of human pathogenic viruses is an indispensable yet rarely studied aspect for sustainable treatment of domestic wastewater by anaerobic membrane bioreactor (AnMBR). In this study, the interface behaviors and removal mechanisms of norovirus genogroup I (GI), genogroup II (GII), and rotavirus A from domestic wastewater was systematically investigated in a one-stage AnMBR. On average, norovirus GI, GII and rotavirus were reduced by 4.64, 5.00, and 2.31 logs, respectively. Viruses tended to be transferred to larger-sized suspended solids from sewage influent to the mixed liquor, and the weight-specific concentration of the virus in >100 µm particles of the mixed liquor was significantly higher than that of sewage, indicating a particle scale-dependent affinity with the virus. In-series membrane filtration test showed the main contribution of the membrane retention, which was dominated by the bio-cake layer and the pristine membrane, while the membrane and associated pore foulants can retain viruses in a filtration resistance-efficient way. An unsteady-state mass balance model revealed that free viruses in the bulk liquid of AnMBR were minimally attached to the cake layer but mainly retained by the membrane and pore foulants (>99%). In addition, despite the small virus decay rates in the mixed liquor, the associated contribution increased with run time due to the prolonged sludge retention time. These insights into virus behaviors and removal mechanisms may provide novel regulation strategies for enhanced virus removal by AnMBR.

Virus removal during sewage treatment by anaerobic membrane bioreactor (AnMBR): The role of membrane fouling.

Anaerobic membrane bioreactor (AnMBR) is a low-energy and promising solution for sewage treatment. During the treatment, the fouled membrane of AnMBR is recognized as an important barrier against pathogenic viruses. Here, the role of membrane fouling of an AnMBR at room temperature in the virus removal was investigated using MS2 bacteriophage as a virus surrogate. Results revealed that the virus removal efficiency of AnMBR was in the range of 0.2 to 3.6 logs, gradually increasing with the course of AnMBR operation. Virus removal efficiency was found to be significantly correlated with transmembrane pressure (R2=0.92, p<0.01), especially in the rapid fouling stage, indicating that membrane fouling was the key factor in the virus removal. The proportion of virus decreased from 52.03% to 15.04% in the membrane foulants when membrane fouling was aggravating rapidly, yet increased from 0.74% to 21.52% in the mixed liquor. Meanwhile, the permeate flux dramatically dropped. These imply that the primary rejection mechanism of virus by membrane in the slow fouling stage is the virus adsorption onto membrane, while the sieving effect is the main reason in the rapid fouling stage. Ex-situ virus rejection test unveiled that the cake layer was the main contributor to the overall virus rejection, while the greatest resistance-specific virus rejection was provided by the organic pore blocking. This paper provides operation strategies to balance enhanced virus removal and high permeate flux by regulating the membrane fouling process.

Protocol for reading and imaging live-cell PKA activity using ExRai-AKAR2.

Fluorescent protein (FP)-based kinase activity biosensors are powerful tools for probing the spatiotemporal dynamics of signaling pathways in living cells. Yet, the limited sensitivity of most kinase biosensors restricts their reliable application in high-throughput detection modalities. Here, we report a protocol for using an ultrasensitive excitation-ratiometric PKA activity reporter, ExRai-AKAR2, to detect live-cell PKA activity via fluorescence microplate reading and epifluorescence microscopy. The high sensitivity of ExRai-AKAR2 is well suited to these high-throughput applications. For complete details on the use and execution of this protocol, please refer to Mehta et al. (2018) andZhang et al., 2021a) .

Long term usage of dexamethasone accelerating accelerates the initiation of osteoarthritis via enhancing chondrocyte apoptosis and the extracellular matrix calcification and apoptosis of chondrocytes.

Systemic application of glucocorticoids is an essential anti-inflammatory and immune-modulating therapy for severe inflammatory or autoimmunity conditions. However, its long-term effects on articular cartilage of patients' health need to be further investigated. In this study, we studied the effects of dexamethasone (Dex) on the homeostasis of articular cartilage and the progress of destabilization of medial meniscus (DMM)-induced osteoarthritis (OA) in adult mice. Long-term administration of Dex aggravates the proteoglycan loss of articular cartilage and drastically accelerates cartilage degeneration under surgically induced OA conditions. In addition, Dex increases calcium content in calcified cartilage layer of mice and the samples from OA patients with a history of long-term Dex treatment. Moreover, long term usage of Dex results in decrease subchondral bone mass and bone density. Further studies showed that Dex leads to calcification of extracellular matrix of chondrocytes partially through activation of AKT, as well as promotes apoptosis of chondrocytes in calcified cartilage layer. Besides, Dex weakens the stress-response autophagy with the passage of time. Taken together, our data indicate that long-term application of Dex may predispose patients to OA and or even accelerate the OA disease progression development of OA patients.

Treatment of idiopathic granulomatous mastitis using ultrasound-guided microwave ablation: a report of 50 cases.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ultrasound-guided microwave ablation combined with glucocorticoid therapy for treating idiopathic granulomatous mastitis (IGM). METHODS: From June 2017 to March 2020, 50 consecutive patients diagnosed with IGM using puncture histology were included. All patients received prednisone and ultrasound-guided microwave ablation and were closely monitored for 12-15 months. RESULTS: A total of 222 lesions in 50 patients were ablated. The results indicated that 78% of cases were cured within 12 months and an additional 20% were cured within 15 months; the recurrence rate was 2%. The clinical and pathological remission rate of the entire group was 98%. The main postoperative complications were local pain, skin ulcerations and sinus formation, skin and areola heat damage, subcutaneous congestion, and fat liquefaction, all of which were conservatively treated. CONCLUSION: Microwave ablation combined with glucocorticoid therapy was safe and effective for the treatment of IGM, with a low recurrence rate. In addition, the cosmetic appearance of the affected breast was preserved with little trauma. Therefore, microwave ablation is a viable method that can be successfully applied in clinical practice.

Ultrasound-guided microwave ablation for multiple benign breast lesions: A prospective study.

AIM: To provide medical evidence for the feasibility and clinical efficacy of microwave ablation (MWA) in the treatment of benign breast lesions, especially multiple benign breast lesions. METHODS: We included patients with multiple benign breast lesions who were seen at our hospital during the period from June 2016 to December 2017. After signed informed consent had been obtained and core breast biopsy, all included patients who underwent MWA at 2450 MHz with 30 W power adjustment. Postoperative follow-up was performed for 1 year, at 3-month intervals. Ablation time, complications, volume-reduction ratio (VRR), and lesion residuals after ablation were analyzed. RESULTS: We ultimately included 1274 lesions from 164 cases in the study with a median follow-up time of 13.6 months. For a single lesion, the median ablation time was 36 s. Pain, fat liquefaction, and skin scalding were the most common complications. The overall complete disappearance rate was 92.1% (1173/1274), with the highest complete disappearance rate observed among those patients with lesions <10 mm in diameter (942/968, 97.3%). For lesions that persisted at 12 months after MWA, the average the volume-reduction ratio (VRR) was 87.5%. CONCLUSIONS: For multiple benign lesions of the breast, especially lesions with the longest diameter <10 mm, ultrasound guided MWA is a minimally invasive, relatively quick therapeutic strategy associated with accuracy in treatment and few complications.

TGF-ß/Alk5 signaling prevents osteoarthritis initiation via regulating the senescence of articular cartilage stem cells.

Osteoarthritis (OA) is the most common joint disease. The surface of joint cartilage is a defensive and first affected structure of articular cartilage (AC) during the pathogenesis of OA. Alk5 signaling is critical for maintaining AC homeostasis, however, the role and underlying mechanism for the involvement of Alk5 signaling in the phenotypes of articular cartilage stem cells (ACSCs) at the surface of AC is still unclear. The role of Alk5 in OA development was explored using an ACSCs-specific Alk5-deficient (cKO) mouse model. Alterations in cartilage structure were evaluated histologically. Senescence was detected by SA-ß-gal, while reactive oxygen species (ROS), MitoTracker, and LysoTracker staining were used to detect changes related to senescence. In addition, mice were injected intra-articularly with ganciclovir to limit the detrimental roles of senescent cells (SnCs). Alk5 cKO mice showed a decreased number of the slow-cell cycle cells and less lubricant secretion at the surface accompanied with drastically accelerated cartilage degeneration under ageing and surgically induced OA conditions. Further studies showed that Alk5 deficient ACSCs exhibited senescence-like manifestations including decreased proliferation and differentiation, more SA-ß-gal-positive cells and ROS production, as well as significantly swollen mitochondria and lysosome breakdown. We further found that local limitation of the detrimental roles of SnCs can attenuate the development of posttraumatic OA. Taken together, our findings suggest that Alk5 signaling acts as an important regulator of the SnCs in the superficial layer during AC maintenance and OA initiation.