MTCH2 in Metabolic Diseases, Neurodegenerative Diseases, Cancers, Embryonic Development and Reproduction.

Mitochondrial carrier homolog 2 (MTCH2) is a member of the solute carrier 25 family, located on the outer mitochondrial membrane. MTCH2 was first identified in 2000. The development in MTCH2 research is rapidly increasing. The most well-known role of MTCH2 is linking to the pro-apoptosis BID to facilitate mitochondrial apoptosis. Genetic variants in MTCH2 have been investigated for their association with metabolic and neurodegenerative diseases, however, no intervention or therapeutic suggestions were provided. Recent studies revealed the physiological and pathological function of MTCH2 in metabolic diseases, neurodegenerative diseases, cancers, embryonic development and reproduction via regulating mitochondrial apoptosis, metabolic shift between glycolysis and oxidative phosphorylation, mitochondrial fusion/fission, epithelial-mesenchymal transition, etc. This review endeavors to assess a total of 131 published articles to summarise the structure and physiological/pathological role of MTCH2, which has not previously been conducted. This review concludes that MTCH2 plays a crucial role in metabolic diseases, neurodegenerative diseases, cancers, embryonic development and reproduction, and the predominant molecular mechanism is regulation of mitochondrial function. This review gives a comprehensive state of current knowledgement on MTCH2, which will promote the therapeutic research of MTCH2.

Canonical and Noncanonical Functions of the BH3 Domain Protein Bid in Apoptosis, Oncogenesis, Cancer Therapeutics, and Aging.

Effective cancer therapy with limited adverse effects is a major challenge in the medical field. This is especially complicated by the development of acquired chemoresistance. Understanding the mechanisms that underlie these processes remains a major effort in cancer research. In this review, we focus on the dual role that Bid protein plays in apoptotic cell death via the mitochondrial pathway, in oncogenesis and in cancer therapeutics. The BH3 domain in Bid and the anti-apoptotic mitochondrial proteins (Bcl-2, Bcl-XL, mitochondrial ATR) it associates with at the outer mitochondrial membrane provides us with a viable target in cancer therapy. We will discuss the roles of Bid, mitochondrial ATR, and other anti-apoptotic proteins in intrinsic apoptosis, exploring how their interaction sustains cellular viability despite the initiation of upstream death signals. The unexpected upregulation of this Bid protein in cancer cells can also be instrumental in explaining the mechanisms behind acquired chemoresistance. The stable protein associations at the mitochondria between tBid and anti-apoptotic mitochondrial ATR play a crucial role in maintaining the viability of cancer cells, suggesting a novel mechanism to induce cancer cell apoptosis by freeing tBid from the ATR associations at mitochondria.

Exosome-Mediated Communication in Thyroid Cancer: Implications for Prognosis and Therapeutic Targets.

Thyroid cancer (THCA) is one of the most common malignancies of the endocrine system. Exosomes have significant value in performing molecular treatments, evaluating the diagnosis and determining tumor prognosis. Thus, the identification of exosome-related genes could be valuable for the diagnosis and potential treatment of THCA. In this study, we examined a set of exosome-related differentially expressed genes (DEGs) (BIRC5, POSTN, TGFBR1, DUSP1, BID, and FGFR2) by taking the intersection between the DEGs of the TCGA-THCA and GeneCards datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the exosome-related DEGs indicated that these genes were involved in certain biological functions and pathways. Protein‒protein interaction (PPI), mRNA‒miRNA, and mRNA-TF interaction networks were constructed using the 6 exosome-related DEGs as hub genes. Furthermore, we analyzed the correlation between the 6 exosome-related DEGs and immune infiltration. The Genomics of Drug Sensitivity in Cancer (GDSC), the Cancer Cell Line Encyclopedia (CCLE), and the CellMiner database were used to elucidate the relationship between the exosome-related DEGs and drug sensitivity. In addition, we verified that both POSTN and BID were upregulated in papillary thyroid cancer (PTC) patients and that their expression was correlated with cancer progression. The POSTN and BID protein expression levels were further examined in THCA cell lines. These findings provide insights into exosome-related clinical trials and drug development.

Highly expressed of BID indicates poor prognosis and mediates different tumor microenvironment characteristics in clear cell renal cell carcinoma.

BACKGROUND: Studies have found that BH3 interacting domain death agonist (BID) is closely related to the occurrence and development of many kinds of tumors. However, little attention has been paid to the situation of BID in clear cell renal cell carcinoma (ccRCC). So, our aim was to explore the effect of BID in ccRCC. METHODS: Survival analysis, ROC curve, correlation analysis and Cox regression analysis were executed to analyze the prognostic value and clinical correlation of BID in ccRCC. The risk prognosis model was constructed in the training cohort and further validated in the internal testing cohort, ICGC cohort, and GEO cohort. Transcriptome sequencing and immunohistochemical staining of clinical specimens were used to validate the results of bioinformatics analysis. The GSEA, ESTIMATE algorithm, CIBERSORT algorithm, ssGSEA, TIDE score, correlation and difference analysis were used to analyze the effects of BID on immune infiltration in tumor microenvironment (TME). RESULTS: BID was highly expressed in ccRCC tissues, which was verified by transcriptome sequencing and immunohistochemical staining of clinical specimens. Patients with high expression of BID had a worse prognosis. BID is an independent prognostic factor for ccRCC. The prognostic model based on BID can accurately predict the prognosis of patients in different cohorts. In addition, the expression levels of BID was closely related to immunomodulatory molecules such as PD-1, LAG3, and CTLA4. Enrichment analysis indicated that BID was significantly enriched in immune-related responses and cancer-related pathways. The change of BID expression mediates different characteristics of immune infiltration in TME. CONCLUSIONS: BID is highly expressed in ccRCC, which is a reliable biomarker of ccRCC prognosis. It is closely related to TME, and may be a potential target for immunotherapy in patients with ccRCC.

Dissecting caspase-2-mediated cell death: from intrinsic PIDDosome activation to chemical modulation.

Caspase-2, a highly conserved member of the caspase family, is considered an initiator caspase that triggers apoptosis in response to some cellular stresses. Previous studies suggest that an intracellular multi-protein complex PIDDosome, induced by genotoxic stress, serves as a platform for caspase-2 activation. However, due to caspase-2's inability to process effector caspases, the mechanism underlying caspase-2-mediated cell death upon PIDDosome activation remains unclear. Here we conducted an unbiased genome-wide genetic screen and identified that the Bcl2 family protein BID is required for PIDDosome-induced, caspase-2-mediated apoptosis. PIDDosome-activated caspase-2 directly and functionally processes BID to signal the mitochondrial pathway for apoptosis induction. Additionally, a designed chemical screen identified a compound, HUHS015, that specifically activates caspase-2-mediated apoptosis. HUHS015-stimulated apoptosis also requires BID but is independent of the PIDDosome. Through extensive structure-activity relationship efforts, we identified a derivative with a potency of ~ 60 nmol/L in activating caspase-2-mediated apoptosis. The HUHS015-series of compounds act as efficient agonists that directly target the interdomain linker in caspase-2, representing a new mode of initiator caspase activation. Human and mouse caspase-2 differ in two crucial residues in the linker, rendering a selectivity of the agonists for human caspase-2. The caspase-2 agonists are valuable tools to explore the physiological roles of caspase-2-mediated cell death and a base for developing small-molecule drugs for relevant diseases.

miR-331-5p Affects Motility of Thyroid Cancer Cell Lines and Regulates BID Expression.

During tumorigenesis, miRNAs with unbalanced expression profiles can increase the threat of disease progression. Here, we focus on the role of miR-331-5p in the pathogenesis of thyroid cancer (TC). In vitro studies were conducted using TC cell lines after the forced expression and silencing of miR-331-5p. Cell proliferation and viability were analyzed via cell counts and colorimetric assays. Cell motility was analyzed via wound healing assays, Transwell migration and invasion assays, and Matrigel Matrix assays. The putative targets of miR-331-5p were unveiled via label-free proteomic screening and then verified using Western blot and luciferase assays. Expression studies were conducted by interrogating The Cancer Genome Atlas (TCGA). We found that ectopic miR-331-5p expression reduces TC cell motility, while miR-331-5p silencing induces the opposite phenotype. Proteomic screening revealed eight putative downregulated targets of miR-331-5p, among which BID was confirmed as a direct target. TCGA data showed the downregulation of miR-331-5p and the upregulation of BID in TC tissues. In summary, deregulation of the miR-331-5p/BID axis could enhance the aggressiveness of TC cell lines, providing new insights into the mechanisms of the progression of this disease and suggesting a potential role of the component factors as possible biomarkers in TC tissues.

MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4.

Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases.

Fostering Flexibility: How Medicare Advantage Potentially Accelerated Telehealth Benefits.

In 2018, the US Congress enacted a policy permitting Medicare Advantage (MA) plans to cover telehealth services in a beneficiary's home and through audio-only means as part of the basic benefit package of services, where prior to the policy change such benefits were only allowed to be covered as a supplemental benefit. MA plans were afforded 2 years of lead time for strategizing, negotiating, and capital investment prior to the start date (January 1, 2020) of the new coverage option. Our data analysis found basic benefit telehealth was offered by plans comprising 71% of enrollment in 2020 and increased to 95% in 2021. At the same time, remote access telehealth was offered as a supplemental benefit for 69% of enrollees in 2020, a decrease of 23% compared to 2019. These efforts by MA plans may have enabled traditional Medicare (TM) to leverage an existing telehealth infrastructure as a solution to the access issues created by public health policies requiring sheltering in place and social distancing during the COVID-19 pandemic. The success of this MA policy prompts consideration of additional flexibility beyond the standard basic benefit package, and whether such benefits reduce costs while improving access and/or outcomes in the context of a managed care environment like MA. Subject to oversight, such flexibility could potentially improve value in MA, and facilitate future changes in TM, as appropriate.

Design and performance analysis of an L-shaped radiator and defected ground antenna for enhancing wireless connectivity in brain implants.

Brain implantable wireless microsystems has potential to treat neurological diseases and maintain the quality of life. Highly efficient miniaturized antenna is the fundamental part of BID (brain implantable device) for reliable signaling of data through dissipative intracranial material. In this paper, a patch antenna with L-shaped defected ground is demonstrated. L-shaped radiator contributed to achieve the resonance at 2.45 GHz industrial scientific and medical (ISM) band. Antenna size is reduced to 10 × 10 × 0.25 mm3. The proposed L-shaped ground plane geometry is contributing in improving the radiation performance. |S11| value shifts from 15 dB to 30 dB after modifying the ground plane. Proposed structure attained the gain of -14 dBi when located between the Dura and CSF layers at the depth of 12 mm in human brain model. Full wave simulated antenna prototype is fabricated and measured for performance verification. Impedance bandwidth of 270 MHz and broadside radiation pattern (for transferring maximum electromagnetic energy away from tissue) are maintained by the proposed antenna. Brain tissue safety is ensured by specific absorption rate which is 0.709 W/kg and in compliance with the safety limits of 1.6 W/kg for 1-g averaged tissue. Proposed antenna structure is the promising candidate for medical implant technology.

The Devil in the details: The factors determining the selection of intrazonal congestion management methods across Europe.

The European electricity market is becoming increasingly interconnected, raising questions about how intrazonal congestion management, typically governed by national regulations, interacts with the coupled cross-zonal markets. A major concern is the lack of information regarding intrazonal congestion management methods. This paper addresses this issue by examining different ways in which European transmission system operators (TSOs) use third-party resources to manage congestion in short-term electricity markets. We create a decision-tree-based classification to represent all identified congestion management methods and select three cases for comprehensive evaluation using predefined assessment criteria. While doing so, we identify a trade-off between efficiency and ease of implementation. The balance between these two factors is determined by the severity of the congestion. In a severely congested grid, locational signals are critical, requiring a better alignment between the network representation in the market clearing and the physical network constraints. When the congestion is less severe, TSOs can choose other congestion management methods based on factors such as the predictability of congestion and resource availability. These findings shed light on the complexities of congestion management in an integrated European market and can inform future policy decisions.

Eco-friendly approach for the fabrication of biо copper based superhydrophobic coating on steel metal and its corrosion resistance evaluation.

This study presents an eco-friendly approach for constructing superhydrophobic (S.H.) coatings on steel surfaces. The biо Сu nanoparticles are synthesized using a biоgenic process. Two types of coatings, Ni-Ѕ.Α and Ni-biо Сu-Ѕ.Α, were developed and characterized. The EDX results confirm the successful fabrication of two distinct coatings on the steel substrate: one involving the modification of nickel with stearic acid, Ni-Ѕ.Α, and the other involving the modification of nickel with both bio-Cu and stearic acid, Ni-biо Сu-Ѕ.Α. The SEM results revealed that the S.H. coats exhibit circular microstructures which contribute to the surface roughness. The contact angles of water droplets on the Ni-Ѕ.Α and Ni-biо Сu-Ѕ.Α coatings were measured at 158° ± 0.9° and 162° ± 1.1°, respectively. Chemical stability tests demonstrated that the Ni-Ѕ.Α coating maintains its S.H. behaviour in a pH range of 3-11, whereas the Ni-biо Сu-Ѕ.Α coating exhibits excellent chemical stability in a broader range of pH (1-13). The coating's mechanical stability was evaluated through abrasion tests. The Ni-Ѕ.Α coating retained its S.H. properties even after an abrasion length equal 1100 mm, while the Ni-biо Сu-Ѕ.Α coating maintained its S.H. behaviour till an abrasion length equal 1900 mm. The corrosion behavior and protective properties of the S.H. coatings were studied via electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP) techniques. The PDP and EIS findings demonstrated that both Ni-Ѕ.Α and Ni-biо Сu-Ѕ.Α coatings significantly reduced the corrosion rate compared to uncoated steel.

The allocative efficiency of construction land quota in rural China: a perspective of bidders' behavior and regret psychology.

The construction land quota pricing mechanism with cost plus pricing method is not sufficient to reflect its intrinsic value. This diminishes the willingness of farmers to voluntarily reclaim abandoned residential and other rural construction land, leading to suboptimal efficiency in rural land utilization and an excessive squandering of rural land resources. Thus, a sequential auction model with two stages for complementary goods was constructed, which considered the synergic characteristics between the land and quota. Further, regret psychology of bidder was considered in the case of winning or losing. A rational pricing mechanism has been developed to allocate construction land quotas, aiming to enhance farmers' motivation to the vacant homesteads of reclamation and revitalizing the stock of rural construction land. The results revealed that the regret psychology in the case of winning would decrease the transaction price of the quota, i.e., the greater the perceived regret in the case of winning, the more significant the reduction in the bidding price offered. Moreover, the regret psychology in the event of losing/failure would increase the transaction price of quota. Furthermore, publishing only the winner's price after the auction leads to the highest price of the quota offered by the bidder. In contrast, publishing only the loser's bidding price leads to the lowest transaction price of the quota offered by the bidder. In addition, the fee for delayed construction would increase the bidding price of the construction land quota. Therefore, local governments should consider announcing only the winner of price after the quota auction has ended. In addition, imposing a fee for delayed construction would enhance the transaction price of land quota, increase farmers' revenue from land reclamation, and incentivize farmers to reclaim unused rural land.

Naringenin-induced Oral Cancer Cell Apoptosis Via ROS-mediated Bid and Bcl-xl Signaling Pathway.

BACKGROUND: Oral cancer is a malignant tumor with a high impact and poor prognosis. Naringenin, a flavonoid found in citrus fruits and its anti-inflammatory and antioxidant properties offer potential therapeutic benefits. However, limited studies have been conducted on the impact of naringenin on human tongue carcinoma CAL-27 cells. This study aims to elucidate the correlation between naringenin and tongue cancer, thereby identifying a potential therapeutic candidate for drug intervention against tongue cancer. METHODS: The effect of naringenin on the apoptosis of CAL-27 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-- FITC apoptosis detection, cell cycle, and apoptosis analysis, Reactive Oxygen Species assay and Western blot. RESULTS: The results showed that naringenin significantly induced apoptosis in CAL-27 cells in a dose-dependent manner. Mechanistically, naringenin-induced apoptosis was mediated through the upregulation of Bid and downregulation of Bcl-xl, which led to increased generation of ROS. CONCLUSION: The findings suggested that naringenin may represent a promising candidate for the treatment of oral cancer by inducing apoptotic cell death via modulation of the Bid and Bcl-xl signaling pathways.

Smartphone use and its association with body image distortion and weight loss behaviours among adolescents in Saudi Arabia.

BACKGROUND: Concerns about the harmful effects of smartphone use on teenage development have been raised as the use of cell phones among adolescents has risen. OBJECTIVE: This study aimed to examine the associations of smartphone usage patterns with Body Image Distortion (BID) and weight loss behaviors among adolescent smartphone users in Saudi Arabia. METHODS: This population-based, cross-sectional study was conducted from July to October 2022. We assessed the mean daily length of smartphone use and classified it into quartiles using data from a self-reported survey and data on weekday and weekend use. Self-reported body weight and height were collected via an online survey. Out of the 11384 adolescents, the majority was females (65.7%) and was secondary school students (68.9%). RESULTS: The prolonged smartphone use (301 min/d) was found in 36.4% of adolescents, 181-300 min/d in 27.6% of respondents, 121-180 min/d in 22.4% of respondents, while the modest smartphone use (1-120 min/d) was found only in 13.6% of participants. The duration of smartphone use was significantly associated with BID (P= 0.000); students with middle perceived stress levels (51.4%) and no depressive symptoms (68.9%) used smartphones 121-180 min/d sparingly. However, prolonged smartphone use was significantly associated with the presence of depressive symptoms (42.6%) and high perceived stress levels (21.5%). Weight loss behaviors were significantly associated with smartphone use duration. Modest smartphone use was significantly found in students with normal weight (P= 0.00, 71.9%); however, aerobic physical activity weight loss strategy (P= 0.00, 30.9%) was correlated with prolonged smartphone use. CONCLUSION: Adequate parental advice is required to assist teenagers in developing healthy smartphone usage practices. Digital platform companies may increase their social responsibility for the information generated and delivered on their networks, boosting its beneficial effect.

Dynamic Interactions between Diarrhoeagenic Enteroaggregative Escherichia coli and Presumptive Probiotic Bacteria: Implications for Gastrointestinal Health.

This study delves into the temporal dynamics of bacterial interactions in the gastrointestinal tract, focusing on how probiotic strains and pathogenic bacteria influence each other and human health. This research explores adhesion, competitive exclusion, displacement, and inhibition of selected diarrhoeagenic Escherichia coli (D-EAEC) and potential probiotic strains under various conditions. Key findings reveal that adhesion is time-dependent, with both D-EAEC K2 and probiotic L. plantarum FS2 showing increased adhesion over time. Surprisingly, L. plantarum FS2 outperformed D-EAEC K2 in adhesion and exhibited competitive exclusion and displacement, with inhibition of adhesion surpassing competitive exclusion. This highlights probiotics' potential to slow pathogen attachment when not in competition. Pre-infecting with L. plantarum FS2 before pathogenic infection effectively inhibited adhesion, indicating probiotics' ability to prevent pathogen attachment. Additionally, adhesion correlated strongly with interleukin-8 (IL-8) secretion, linking it to the host's inflammatory response. Conversely, IL-8 secretion negatively correlated with trans-epithelial electrical resistance (TEER), suggesting a connection between tight junction disruption and increased inflammation. These insights offer valuable knowledge about the temporal dynamics of gut bacteria interactions and highlight probiotics' potential in competitive exclusion and inhibiting pathogenic bacteria, contributing to strategies for maintaining gastrointestinal health and preventing infections.

Unlocking the secrets of exchange rate determination in Malaysia: A Game-Changing hybrid model.

Nominal exchange rate determination is a puzzling phenomenon throughout the literature. Thus, the study aims to analyze the nominal exchange rate determination with a hybrid approach of macroeconomic and microstructure determinants, i.e., interest rate differential, oil price, order flow, and bid-ask spread over the long- and short-run horizons in the context of Malaysia. The dataset consists of high-frequency daily data from 2010 to 2017, employing a nonlinear ARDL approach. The results indicate that the bid-ask spread and interest rate differential were found to be key determinants of exchange rate dynamics in the long and short run. The findings show strong evidence of long-run asymmetry in the interest rate differential, while short-run asymmetry effects exist between microstructure determinants and the exchange rate. In addition, it indicates that the bid-ask spread holds informative content to explain the dynamics of the exchange rate in Malaysia. Additionally, the negative changes in the oil price could potentially act as macroeconomic news announcements and the bid-ask spread as liquidity determinants in Malaysia, which play a significant role in exchange rate determination. The study concluded that the prominent short-run asymmetry effects captured in cumulative order flow and bid-ask spread While a long-run asymmetry exists between the oil price and exchange rate in Malaysia. The empirical results allow for long-run and short-run asymmetric pricing impacts of a hybrid approach on the nominal exchange rate in Malaysia. This study is helpful in providing policy direction and practical implications for monetary authorities and market dealers. The bid-ask spread and oil price could be considered influential exchange rate determinants in the short run in Malaysia.

A Novel Foodborne Illness Detection and Web Application Tool Based on Social Media.

Foodborne diseases and outbreaks are significant threats to public health, resulting in millions of illnesses and deaths worldwide each year. Traditional foodborne disease surveillance systems rely on data from healthcare facilities, laboratories, and government agencies to monitor and control outbreaks. Recently, there is a growing recognition of the potential value of incorporating social media data into surveillance systems. This paper explores the use of social media data as an alternative surveillance tool for foodborne diseases by collecting large-scale Twitter data, building food safety data storage models, and developing a novel frontend foodborne illness surveillance system. Descriptive and predictive analyses of the collected data were conducted in comparison with ground truth data reported by the U.S. Centers for Disease Control and Prevention (CDC). The results indicate that the most implicated food categories and the distributions from both Twitter and the CDC were similar. The system developed with Twitter data could complement traditional foodborne disease surveillance systems by providing near-real-time information on foodborne illnesses, implicated foods, symptoms, locations, and other information critical for detecting a potential foodborne outbreak.

BID expression determines the apoptotic fate of cancer cells after abrogation of the spindle assembly checkpoint by AURKB or TTK inhibitors.

BACKGROUND: Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection. METHODS: A panel of 53 tumor cell lines of different origins was used. The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Finally, in vivo experiments were performed by implanting cultured cells or fragments of tumors into immunodeficient mice. RESULTS: Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. SAC abrogation induced activation of CASP-2, leading to cleavage of CASP-3 and extensive cell death only in presence of high levels of BID. Finally, a prevalence study revealed high BID mRNA in 6% of human solid tumors. CONCLUSIONS: The fate of tumor cells after SAC abrogation is driven by an AURKB/ CASP-2 signaling mechanism, regulated by BID levels. Our results pave the way to clinically explore SAC-targeting drugs in tumors with high BID expression.

Tsetse fly inspired steerable bone drill-a proof of concept.

The fixation strength of pedicle screws could be increased by fixating along the much stronger cortical bone layer, which is not possible with the current rigid and straight bone drills. Inspired by the tsetse fly, a single-plane steerable bone drill was developed. The drill has a flexible transmission using two stacked leaf springs such that the drill is flexible in one plane and can drill along the cortical bone layer utilizing wall guidance. A proof-of-principle experiment was performed which showed that the Tsetse Drill was able to successfully drill through 5, 10 and 15 PCF cancellous bone phantom which has similar mechanical properties to severe osteoporotic, osteoporotic and healthy cancellous bone. Furthermore, the Tsetse Drill was able to successfully steer and drill along the cortical wall utilizing wall guidance for an insertion angle of 5°, 10° and 15°. The experiments conclude that the tsetse fly-inspired drilling method is successful and even allows the drilling along the cortical bone layer. The Tsetse Drill can create curved tunnels utilizing wall guidance which could increase the fixation strength of bone anchors and limit the risk of cortical breach and damage to surrounding anatomy.

Do COVID-19 pandemic-related policy shocks flatten the bid-rent curve? Evidence from real estate markets in Shanghai.

The COVID-19 pandemic has drastically affected the socioeconomic activities and peoples' daily life, resulting in a change in locational preferences in the real estate markets. Although enormous efforts have been devoted to examining the housing price impacts of the COVID-19 pandemic, little is known about the responses of the real estate markets to the evolving pandemic control measures. This study investigates the price gradient effects of various pandemic-related policy shocks using a hedonic price model on the district-level property transaction data in Shanghai, China over a 48-month period from 2018 to 2021. We found that these shocks have significantly altered the bid-rent curves. The price gradient for residential property units decreased in absolute value to - 0.433 after Wuhan's lockdown, demonstrating peoples' preferences to avoid the high infection risks in districts closer to the city center. However, in the post-reopening and post-vaccine periods, the price gradient increased to - 0.463 and - 0.486, respectively, implying rational expectations of a recovering real estate market for the low infection and mortality rates. In addition, we discovered that Wuhan's lockdown has steepened the price gradient for commercial property units, suggesting a decline in business volumes and an increase in operating costs in the low-density districts imposed by the strict pandemic control measures. This study contributes to the empirical literature on the price gradient effects of the COVID-19 pandemic by extending the study period to the post-vaccine era.