Atmosphere teleconnections from abatement of China aerosol emissions exacerbate Northeast Pacific warm blob events.

During 2010 to 2020, Northeast Pacific (NEP) sea surface temperature (SST) experienced the warmest decade ever recorded, manifested in several extreme marine heatwaves, referred to as "warm blob" events, which severely affect marine ecosystems and extreme weather along the west coast of North America. While year-to-year internal climate variability has been suggested as a cause of individual events, the causes of the continuous dramatic NEP SST warming remain elusive. Here, we show that other than the greenhouse gas (GHG) forcing, rapid aerosol abatement in China over the period likely plays an important role. Anomalous tropospheric warming induced by declining aerosols in China generated atmospheric teleconnections from East Asia to the NEP, featuring an intensified and southward-shifted Aleutian Low. The associated atmospheric circulation anomaly weakens the climatological westerlies in the NEP and warms the SST there by suppressing the evaporative cooling. The aerosol-induced mean warming of the NEP SST, along with internal climate variability and the GHG-induced warming, made the warm blob events more frequent and intense during 2010 to 2020. As anthropogenic aerosol emissions continue to decrease, there is likely to be an increase in NEP warm blob events, disproportionately large beyond the direct radiative effects.

Responsive regularity of neurons in the hindlimb region of primary somatosensory cortex to different temperature thermal needle stimulation of "Zusanli"(ST36) in mice. / å°é¼ åˆçº§ä½“æ„Ÿçš®å±‚åŽè‚¢åŒºç¥žç»å ƒå¯¹"足三里"不同温度热刺激的响应规律.

OBJECTIVES: To study the regularity of central response to thermal needle stimulation of "Zusanli" (ST36) at different temperature, and to analyze the temperature difference of central responses. METHODS: Six male C57BL/6j adult mice were used in the present study. For observing activities of neurons in the hindlimb region of left primary somatosensory cortex (S1HL, A/P=0.46 mm, M/L=1.32 mm, D/V=-0.14 mm) by using a fast high-resolution miniature two-photon microscopy (FHIRM-TPM), the mice were anesthetized with 3% isoflurane (inhalation), with its head fixed in a stereotaxic apparatus, then, adeno-associated virus (AAV-hSyn-GCaMP6f-WPRE-hGHpA, for showing intracellular calcium transients in neurons transfected) was injected into the left S1HL region using a micro-syringe after scalp surgical operation. The mice's right ST36 were stimulated using internal thermal needles with the temperature being 43 ℃, or 45 ℃, or 47 ℃, separately. Image J software and MATLAB 2020b software were used to process the image data of neuronal calcium activity (Ca2+ signaling) in the left S1HL region, including the instant maximum calcium peak value (ΔF/F) in 2 s, instant calcium spike frequency in 2 s, short-term calcium peak value (ΔF/F) in 3.5 min, short-term calcium spike frequency in 3.5 min, calcium peak duration in 3.5 min, maximum calcium peak value (ΔF/F) at the 1st , 2nd and 3rd min, and calcium spike frequency at the 1st, 2nd and 3rd min after thermal needle stimulation. RESULTS: In comparison with the normal temperature needle stimulation, the instant intracellular maximum calcium peak value, instant calcium spike frequency, short-term maximum calcium peak value, short-term calcium spike frequency, and calcium peak duration of S1HL neurons in response to 43 ℃, 45 ℃ and 47 ℃ internal thermal needle stimulation of ST36 were significantly increased (P<0.001, P<0.01). Comparison among the 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation showed that the 45 ℃ thermal needle stimulation was obviously superior to 43 ℃ and 47 ℃ thermal needle stimulation in increasing instant calcium spike frequency, short-term calcium spike frequency and calcium peak duration of S1HL neurons (P<0.001, P<0.01). The 47 ℃ thermal needle stimulation was stronger than 43 ℃ and 45 ℃ thermal needle stimulation in increasing the instant maximum calcium peak value (P<0.001). The maximum calcium peak value was apparently higher (P<0.001) at the 2nd min than that at the 1st and 3rd min after 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation. No significant differences were found in the short-term maximum calcium peak value among the 3 thermal needle stimulation and in the calcium spike frequency among the 3 time points after 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation. CONCLUSIONS: S1HL neurons respond to all 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation of ST36 in mice, while more actively to 45 ℃ thermal needle stimulation.

Comparison of different concentrations of chlorhexidine-iodophor composite solution on human skin fibroblasts.

OBJECTIVE: Chlorhexidine-iodophor (CHX-IP) composite solution is a polymer of chlorhexidine and iodophor produced with new technology, for use in diabetic foot infection. However, the effect of CHX-IP on the growth activity of fibroblasts remains unknown, thus the effects of different concentrations of CHX-IP composite solution on the viability and micromorphology of human skin fibroblasts were studied in vitro cell culture in this study. METHOD: A cell viability assay was applied to calculate cell viability and an inverted fluorescence microscope was used to observe cell morphology over five days. RESULTS: The results showed that the toxic effect of CHX-IP on fibroblasts was solution concentration-dependent and decreased over time. When the concentration of CHX-IP was 5.0mg/ml, 2.5mg/ml, 0.625mg/ml, 0.15625mg/ml, 0.078125mg/ml or 0mg/ml, the difference of optical density (OD) value on different days was statistically significant (p<0.05). There were statistically significant differences in the OD value of fibroblasts among different concentrations of CHX-IP on: day 2 (F=4.809, p=0.004); day 3 (F=21.508, p<0.001); day 4 (F=63.952, p<0.001); and day 5 (F=160.407, p<0.001). In addition, a concentration of 5.0mg/ml CHX-IP resulted in a fibroblastic viability rate of 0% on day 4, when CHX-IP was diluted to 2.5mg/ml or 1.25 mg/ml, fibroblastic viability rate decreased to 0% day 5. However, when the CHX-IP was diluted to 0.15625mg/ml or 0.078125mg/ml, the fibroblastic cell viability rate increased slightly on day 5. The morphology of cells observed under microscope indirectly supported this result. CONCLUSION: The findings of this study showed that the toxic effect of CHX-IP on fibroblasts was solution concentration-dependent and decreased over time.

High-efficiency reinforcement learning with hybrid architecture photonic integrated circuit.

Reinforcement learning (RL) stands as one of the three fundamental paradigms within machine learning and has made a substantial leap to build general-purpose learning systems. However, using traditional electrical computers to simulate agent-environment interactions in RL models consumes tremendous computing resources, posing a significant challenge to the efficiency of RL. Here, we propose a universal framework that utilizes a photonic integrated circuit (PIC) to simulate the interactions in RL for improving the algorithm efficiency. High parallelism and precision on-chip optical interaction calculations are implemented with the assistance of link calibration in the hybrid architecture PIC. By introducing similarity information into the reward function of the RL model, PIC-RL successfully accomplishes perovskite materials synthesis task within a 3472-dimensional state space, resulting in a notable 56% improvement in efficiency. Our results validate the effectiveness of simulating RL algorithm interactions on the PIC platform, highlighting its potential to boost computing power in large-scale and sophisticated RL tasks.

[Source Analysis and Health Risk Assessment of PAHs in PM2.5, Lüliang City].

To investigate the seasonal variation, health risks, and potential sources of polycyclic aromatic hydrocarbons(PAHs) in PM2.5 in the Lüliang area, PM2.5 samples were collected in Lishi District(downtown area) and Xiaoyi City(suburban area) from October 23, 2018 to July 1, 2019, and the concentrations of 14 PAHs were determined using gas chromatography-mass spectrometry(GC-MS). The annual average concentration of PAHs was 95.50 ng·m-3, and the concentration of 5-6 ring PAHs was mainly(49.7%), with 3 ring PAHs accounting for a relatively low proportion(8.3%).The concentration of PAHs in Lüliang City showed a seasonal pattern of winter>autumn>spring>summer. The results of the ILCRs model and Monte Carlo simulation showed that the toxicity of PAHs in Lüliang City followed the rule of adults>youth>children. Except in summer, the ILCRs values in the Lishi area were between 10-6 and 10-4, much higher than those in Xiaoyi City, indicating that there was a high potential risk of polycyclic aromatic hydrocarbons in the urban area. Through the characteristic ratio method and positive matrix factorization(PMF), it was shown that the PAHs in Lüliang City were mainly from the combustion of coal and biomass(61.9%) and vehicle exhaust emissions(38.1%). Based on the backward trajectory and potential source factor contribution analysis model, it was determined that the potential sources of PAHs in Lüliang City were mainly distributed in southern Shanxi, northern Shaanxi, and western Inner Mongolia.

Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons.

Understanding the molecular interaction between ligand and receptor is important for providing the basis for the development of regenerative drugs. Although it has been reported that extracellular phosphoglycerate kinase 1 (Pgk1) can promote the neurite outgrowth of motoneurons, the Pgk1-interacting neural receptor remains unknown. Here we show that neural membranous Enolase-2 exhibits strong affinity with recombinant Pgk1-Flag, which is also evidently demonstrated by immunoelectron microscopy. The 325th-417th domain of Pgk1 interacts with the 405th-431st domain of Enolase-2, but neither Enolase-1 nor Enolase-3, promoting neurite outgrowth. Combining Pgk1 incubation and Enolase-2 overexpression, we demonstrate a highly significant enhancement of neurite outgrowth of motoneurons through a reduced p-P38-T180/p-Limk1-S323/p-Cofilin signaling. Collectively, extracellular Pgk1 interacts neural membrane receptor Enolase-2 to reduce the P38/Limk1/Cofilin signaling which results in promoting neurite outgrowth. The extracellular Pgk1-specific neural receptor found in this study should provide a material for screening potential small molecule drugs that promote motor nerve regeneration.

Chatbot-assisted therapy for patients with methamphetamine use disorder: a preliminary randomized controlled trial.

Background: Methamphetamine (MA) use disorder is associated with a large public health burden. Despite the therapeutic effects of psychosocial interventions based on current evidence, finding an approach to retain patients in treatment remains a real-world challenge. The rapid development of mobile health (mHealth) systems suggests the potential to provide real-time personalized care at any time and from any location, minimize barriers to treatment, maximize use, and promote the dissemination of accessible therapeutic tools in at-risk populations. Our study aimed to investigate the feasibility and effectiveness of chatbots for the treatment of MA use disorder. Method: The inclusion criteria were (a) a diagnosis of MA use disorder as defined by the DSM-5, (b) age between 18 and 65 years, (c) no acute exacerbation of severe mental illness during the initial assessment, such as schizophrenia or bipolar I disorder, (d) willingness to participate in standard outpatient treatment for ≥ 6 months, and (e) an Android phone. Participants were randomly allocated to either a chatbot-assisted therapy via smartphone (CAT) group or a control group following simple randomization procedures (computerized random numbers) without blinding. All participants were followed up for 6 months. Treatment retention and monthly urine test results were analyzed as outcome measures. Participants' satisfaction with CAT was also assessed. Results: In total, 50 and 49 participants were allocated to the CAT and control groups, respectively. There were no significant differences in retention time between the two treatment groups (df = 1, p = 0.099). The CAT group had fewer MA-positive urine samples than the control group (19.5% vs. 29.6%, F = 9.116, p = 0.003). The proportion of MA-positive urine samples was positively correlated with the frequency of MA use (r = 0.323, p = 0.001), severity of MA use disorder (r = 0.364, p < 0.001), and polysubstance use (r = 0.212, p = 0.035), and negatively correlated with readiness to change (r = -0.330, p = 0.001). Totally 55 participants completed the study at the 6-month follow-up and 60% reported relative satisfaction. Conclusion: Participants in this study had favorable acceptance and generally positive outcomes, which indicates that chatbot is feasible for treating people who use MA.

ATFS-1 counteracts mitochondrial DNA damage by promoting repair over transcription.

The ability to balance conflicting functional demands is critical for ensuring organismal survival. The transcription and repair of the mitochondrial genome (mtDNA) requires separate enzymatic activities that can sterically compete1, suggesting a life-long trade-off between these two processes. Here in Caenorhabditis elegans, we find that the bZIP transcription factor ATFS-1/Atf5 (refs. 2,3) regulates this balance in favour of mtDNA repair by localizing to mitochondria and interfering with the assembly of the mitochondrial pre-initiation transcription complex between HMG-5/TFAM and RPOM-1/mtRNAP. ATFS-1-mediated transcriptional inhibition decreases age-dependent mtDNA molecular damage through the DNA glycosylase NTH-1/NTH1, as well as the helicase TWNK-1/TWNK, resulting in an enhancement in the functional longevity of cells and protection against decline in animal behaviour caused by targeted and severe mtDNA damage. Together, our findings reveal that ATFS-1 acts as a molecular focal point for the control of balance between genome expression and maintenance in the mitochondria.

Evaluation on the application effect of "flipped classroom" in general surgery practice teaching / 中华医学教育探索杂志

Objective:To explore the application and practice of "flipped classroom" in the teaching of general surgery interns.Methods:A total of 20 internship groups (3 to 5 people in each group) were randomly selected from the general surgery practice group in the Department of General Surgery of the Second Clinical Medical College of North Sichuan Medical College. They were randomly divided into the flipped group (45 people) and the traditional group (40 people), with 10 subgroups in each group. The flipped group adopted the flipped classroom teaching mode (students' self-study by handing out materials before class, students and teachers' discussion in class, and students and teachers' evaluation after class), while the control group adopted the current conventional teaching mode (students' preview before class, teachers' explanation in class, and teachers' question answering after class). At the end of the teaching, a questionnaire was used to evaluate the participation and completion of each student. The teaching effect was evaluated by medical history collection and case analysis. The participation, completion, and teaching effect between the two groups were compared and analyzed. SPSS 23.0 software was used for t-test and Chi-square test. Results:The participation of the flipped group was better than that of the traditional group [(17.45±1.83) vs. (15.57±1.52)], and the difference was statistically significant ( P < 0.05). There was no statistically significant difference between the flipped group and the traditional group. There was no significant difference in medical history collection scores between the two groups. The case analysis of the flipped group was better than that of the traditional group [(87.30±6.06) vs. (81.50±5.88), P < 0.05]. The questionnaire shows that about 90% of the students think that flipped classroom can improve their interest in learning [96% (43/45)], improve their autonomous learning ability [89% (40/45)], and have better learning effect. At the same time, 78% (35/45) of students think that learning time is too long. Conclusion:The flipped classroom teaching model can improve the teaching participation of general surgery students, improve students' interest in learning, improve their self-learning ability, and improve students' thinking ability of medical record analysis.

Study of The specificity of gut microbiota in adult patients with delayed-onset of atopic dermatitis

Background Atopic dermatitis (AD) is a common and recurrent skin disease. The first onset of AD in adults is known as adult-onset atopic dermatitis (AOAD). Gut microbiota is closely associated with AD, and the “gut–skin” axis is considered as a novel target for prevention of AD. However, only a few studies have analyzed AOAD, particularly the studies that compared differences in intestinal flora between AOAD and persistent AD patients. Objective To investigate main specificities of intestinal microbiota in AOAD patients, particularly comparing with persistent AD patients. Methods A comprehensive taxonomic and functional analysis of gut microbiota in 10 healthy, 12 AOAD, and 10 persistent AD patients was done by using bacterial 16S ribosomal RNA (rRNA) gene analysis. Chao1 and Shannon diversity indices were measured to analyze alpha diversity, and the linear discriminant analysis (LDA) effect size (LEfSe) algorithm was applied to identify differences in genus. Results The alpha diversity of gut microbiota in AOAD patients was decreased, with Escherichia-shigella (15.8%) being the predominant genus of AOAD group. Agathobacter and Dorea in AOAD patients were significantly reduced, whereas the relative level of Bacteroides pectinophilus group was remarkably elevated compared with healthy volunteers and persistent AD patients. Conclusion The present study revealed differences in intestinal flora between AOAD, healthy adults, and non-adult onset of AD, and explored differential dominant bacteria between AOAD and persistent AD patients (AU)

Cylindrical Tube Stethoscopes: The Value of Practical Equipment in the Management of Patients with Infectious Diseases.

Background: The COVID-19 pandemic has continued for more than two years since its outbreak. Due to the clinical auscultation needs of doctors when wearing airtight protective clothing, a cylindrical tube stethoscope was proposed to address this problem. However, the idea has been questioned by some experts. Methods: To address these questions, we performed three-part experiments using cylindrical tube stethoscopes. First, we performed laboratory tests to detect the sound intensity from a cylindrical tube stethoscope. Second, we improved the cylindrical tube stethoscope to achieve better results. Third, we revealed the difference in the auscultation effects of the cylindrical tube stethoscope and a conventional professional 3 M stethoscope. Results: From these experiments, we found that a narrow cylindrical tube with a diameter of 4.2 cm and a length of 20 cm equipped with a silicone gasket better auscultation of heart sounds. A cylindrical tube stethoscope and a 3 M stethoscope were used to perform stethoscope tests on 10 volunteers. The alveolar lung sounds were 44.478 decibels vs 49.529 decibels, the heart sounds were 46.631 decibels vs 41.109 decibels, and the intestinal sounds were 40.132 decibels vs 43.787 decibels, respectively. Conclusion: This improved cylindrical tube stethoscope can meet the auscultation requirements for cardiorespiratory and abdominal diagnosis during infectious disease pandemics.

A case report of acute testicular pain secondary to segmental testicular infarction.

BACKGROUND: Segmental testicular infarction is a rare condition that often occurs in the upper pole of the left testicle and usually presents with acute onset of scrotal pain. Contrast-enhanced ultrasound and MR are essential for diagnosing and differentiating segmental testicular infarction in clinical practice, and conservative treatment can only be adopted after a definitive diagnosis. In the present case, after conservative treatment, the infarct volume was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. We performed a correlation analysis to investigate the causes of these changes. CASE PRESENTATION: A 33-year-old male, without any specific disease history, was admitted to the hospital with a 5-day history of left testicular pain, and the imaging showed focal necrosis of the left testicle with hemorrhage. He was diagnosed with segmental testicular infarction after differentiating and excluding it from malignant tumors. Conservative medical treatment was given, and the symptoms of testicular pain were relieved after treatment. After discharge, regular reexamination at follow-ups showed that the infarct's size was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. CONCLUSION: Conservative treatment has become the standard treatment currently adopted after confirming the diagnosis of segmental testicular infarction through contrast-enhanced ultrasound and MR. The blood flow changes in and around the focus of testicular infarction can be related to various factors. At present, relevant conclusions of the underlying mechanisms were mainly deduced from infarction studies of other related organs such as the heart and brain; thus, the specific pathological mechanism needs further experimental verification.

Is acupuncture effective for knee osteoarthritis? A protocol for a systematic review and meta-analysis.

INTRODUCTION: Knee osteoarthritis (KOA) is one of the leading causes of disability. The effectiveness of acupuncture for treating KOA remains controversial. This protocol describes the method of a systematic review and meta-analysis evaluating the effectiveness and safety of acupuncture for treating KOA. METHODS AND ANALYSIS: Four English databases (PubMed, Embase, Cochrane Library databases and Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, and Wanfang) will be searched from the database inception to 1 September 2021. All randomised controlled trials related to acupuncture for KOA will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be pain intensity. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The strength of recommendations and quality of evidence will be assessed using the Grading of Recommendations Assessment Development and Evaluation working group methodology. ETHICS AND DISSEMINATION: Ethics approval is not required because individual patient data are not included. This protocol was registered in the international Prospective Register of Systematic Reviews on 25 February 2021. The systematic review and meta-analysis will be submitted for publication in a peer-reviewed journal. The findings will also be disseminated through conference presentations. TRIAL REGISTRATION NUMBER: CRD42021232177.

Influence of calcareous nodules content on scaling effect in shear strength of cohesive soil containing calcareous nodules.

The difference in the shear strength and other characteristics of the cohesive soil containing calcareous nodules (CSCN) between samples with large size and corresponding scaling size, which is called scaling effect, is significantly affected by its calcareous nodule content (CNC) of the gradation composition. However, current researches rarely reveal the influence of the CNC on the scaling effect in shear strength of samples. In this study, how and why the CNC affects the scaling effect in shear strength were explored. Then a method to reduce the scaling effect based on the reason for influence was proposed. Results show that the correlation between the scaling effect in shear strength and the CNC presents a step curve. This is attributed to that it is easier to form a skeleton effect in samples with scaling size for the same CNC. Considering the skeleton effect, a calculation model for the shear strength parameters of CSCN samples with large size is proposed to reduce the scaling effect. This paper demonstrates that the proposed calculation model provides an access to obtain calculated shear strength parameters of CSCN samples with large size by using measured results of samples with corresponding scaling size.

Study on improving the diagnostic performance of transrectal ultrasound for prostate cancer diagnosis based on deep learning / 中华超声影像学杂志

Objective:To explore the application value of transrectal ultrasound images classification network model of prostate cancer based on deep learning in the classification of benign and malignant prostate tissue in transrectal ultrasound images.Methods:A total of 1 462 two-dimensional images of transrectal prostate biopsy with clear pathologic results(including 658 images of malignant tumor, 804 images of benign tumor) from 203 patients with suspicious prostate cancer(including 89 cases of malignant tumor, 114 cases of benign tumor) were collected from May 2018 to May 2021 in the First Affiliated Hospital of Jinan University. They were divided into the training database, validation database, and test database. And the training and validation database were used to train and obtain the intelligence-assisted diagnosis network model, and then the test database was used to test the network model and two ultrasound doctors of different ages. With pathologic diagnosis as the gold standard, the diagnostic performance among them was evaluated.Results:①The sensitivity of network model was 66.7% the specificity was 91.9%, the accuracy was 80.5%, the precision(positive predictive value) was 87.1%. The area under the ROC curve was 0.922. ②The accuracy of the junior and senior ultrasound doctors was 57.5%, 62.0%; the specificity was 62.0%, 66.3%; the sensitivity was 51.5%, 56.8%; the precision was 53.1%, 58.1%, respectively. ③The accuracy, sensitivity, specificity, precision of classification: the network model > the ultrasound doctors, the differences were significant( P<0.05); the senior ultrasound doctor>the junior ultrasound doctor, the differences were not significant( P>0.05). Conclusions:The intelligence-assisted diagnosis network model based on deep learning can classify benign and malignant prostate tissue in transrectal ultrasound images, improve the accuracy of ultrasound doctors in diagnosing prostate cancer. It is of great significance to improve the efficiency of screening for patients with high clinical suspicion of prostate cancer.

[Analysis on developmental characteristics of acupoint theory].

The theory of acupoints has gone through a long process from its embryonic form to its maturity, including its gradual improvement in later generations. Starting from the acupuncture literature in different historical periods, we, in the present paper, gave some examples and analyzed the connotation of important concepts in the development of acupoint theory. It is believed that the signs of the establishment of acupoint theory mainly include the standardization of acupoints' names, the specific description of acupoint positioning, the enrichment and explicitation of the content of acupoints' indications, the highlights of the meridian theory via classification of acupoints, and the interpretation of connotations of acupoints from a clinical perspective.

The Role of Non-Coding RNAs in Breast Cancer Drug Resistance.

Breast cancer (BC) is one of the commonly occurring malignancies in females worldwide. Despite significant advances in therapeutics, the mortality and morbidity of BC still lead to low survival and poor prognosis due to the drug resistance. There are certain chemotherapeutic, endocrine, and target medicines often used for BC patients, including anthracyclines, taxanes, docetaxel, cisplatin, and fluorouracil. The drug resistance mechanisms of these medicines are complicated and have not been fully elucidated. It was reported that non-coding RNAs (ncRNAs), such as micro RNAs (miRNA), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) performed key roles in regulating tumor development and mediating therapy resistance. However, the mechanism of these ncRNAs in BC chemotherapeutic, endocrine, and targeted drug resistance was different. This review aims to reveal the mechanism and potential functions of ncRNAs in BC drug resistance and to highlight the ncRNAs as a novel target for achieving improved treatment outcomes for BC patients.

Dark Matter Freeze-Out via Catalyzed Annihilation.

We present a new paradigm of dark matter freeze-out, where the annihilation of dark matter particles is catalyzed. We discuss in detail the regime in which the depletion of dark matter proceeds via 2χ→2A^{'} and 3A^{'}→2χ processes, where χ and A^{'} denote dark matter and the catalyst, respectively. In this regime, the dark matter number density is depleted polynomially rather than exponentially (Boltzmann suppression) as in classical weakly interacting massive particles and strongly interacting massive particles. The paradigm applies for a secluded weakly interacting dark sector with dark matter in the MeV-TeV mass range. The catalyzed annihilation paradigm is compatible with cosmic microwave background and big bang nucleosynthesis constraints, with enhanced indirect detection signals.

Mortalin maintains breast cancer stem cells stemness via activation of Wnt/GSK3ß/ß-catenin signaling pathway.

Previous research indicated that mortalin overexpressed in breast cancer and contributed to carcinogenesis. Mortalin was also demonstrated to promote Epithelial-mesenchymal transition (EMT) and was considered as a factor for maintaining the stemness of the cancer stem cells. However, the underlying mechanisms about mortalin maintaining the stemness of breast cancer stem cells (BCSCs) remain unclear. Here, we identified that increased expression of mortalin in breast cancer was associated with poorer overall survival rate. Mortalin was elevated in breast cancer cell lines and BCSC-enriched populations. Additionally, knockdown of mortalin significantly inhibited the cell proliferation, migration and EMT, as well as sphere forming capacity and stemness genes expression. Further study revealed that mortalin promoted EMT and maintained BCSCs stemness via activating the Wnt/GSK3ß/ß-catenin signaling pathway in vivo and in vitro. Taken together, these findings unveiled the mechanism of mortalin in maintaining and regulating the stemness of BCSCs, and may offer novel therapeutic strategies for breast cancer treatment.

PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome.

In multiple species, certain tissue types are prone to acquiring greater loads of mitochondrial genome (mtDNA) mutations relative to others, but the mechanisms that drive these heteroplasmy differences are unknown. We find that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans. We demonstrate that tissues prone to accumulating ΔmtDNA have lower mitophagy responses than those with low mutation levels. Moreover, we show that ΔmtDNA heteroplasmy increases when proteotoxic species that are associated with neurodegenerative disease and mitophagy inhibition are overexpressed in the nervous system. These results suggest that PINK1 and parkin drive organism-wide patterns of heteroplasmy and provide evidence of a causal link between proteotoxicity, mitophagy, and mtDNA mutation levels in neurons.