Ginsenoside Rg3 decreases breast cancer stem-like phenotypes through impairing MYC mRNA stability.

Breast cancer stem cells (BCSCs) are responsible for breast cancer metastasis, recurrence and treatment resistance, all of which make BCSCs potential drivers of breast cancer aggression. Ginsenoside Rg3, a traditional Chinese herbal medicine, was reported to have multiple antitumor functions. Here, we revealed a novel effect of Rg3 on BCSCs. Rg3 inhibits breast cancer cell viability in a dose- and time-dependent manner. Importantly, Rg3 suppressed mammosphere formation, reduced the expression of stemness-related transcription factors, including c-Myc, Oct4, Sox2 and Lin28, and diminished ALDH(+) populations. Moreover, tumor-bearing mice treated with Rg3 exhibited robust delay of tumor growth and a decrease in tumor-initiating frequency. In addition, we found that Rg3 suppressed breast cancer stem-like properties mainly through inhibiting MYC expression. Mechanistically, Rg3 accelerated the degradation of MYC mRNA by enhancing the expression of the let-7 family, which was demonstrated to bind to the MYC 3' untranslated region (UTR). In conclusion, our findings reveal the remarkable suppressive effect of Rg3 on BCSCs, suggesting that Rg3 is a promising therapeutic treatment for breast cancer.

Integrated network pharmacology and metabolomics reveal the action mechanisms of vincristine combined with celastrol against colon cancer.

Colon cancer is associated with a high mortality rate. Vincristine (VCR) is a commonly used chemotherapeutic drug. Celastrol (CEL) is an effective component which exerts inhibitory effects on colon cancer. Combination treatment improves resistance to chemotherapeutic drugs and enhances their efficacy. Therefore, we aimed to explore the molecular mechanisms of VCR combined with CEL in colon cancer treatment. We verified the effects of VCR combined with CEL on the proliferation, cell cycle, and apoptosis of HCT-8 cells. Non-targeted metabolomic techniques were used to analyse the changes in cellular metabolites after administration. Finally, network pharmacology technology was used to screen the potential targets and pathways. VCR combined with CEL had synergistic inhibitory effects on HCT-8 colon cancer cells. Cell metabolomics identified 12 metabolites enriched in metabolic pathways, such as the phenylalanine, tyrosine and tryptophan biosynthesis pathways. Network pharmacology revealed that MAPK1, AKT1, PIK3CB, EGFR, and VEGFA were the key targets. Western blotting revealed that VCR combined with CEL activated the P53 pathway by suppressing the PI3K/AKT signalling pathway activation and Bcl-2 expression, promoting the Bax expression. Therefore, VCR combined with CEL potentially treats colon cancer by increasing the apoptosis, improving energy metabolism, and inhibiting PI3K/AKT pathway in colon cancer cells.

FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression.

BACKGROUND: Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear. METHODS: In this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model. RESULTS: FAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs. CONCLUSIONS: In this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer.

FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: Herein, we aimed at exploring the FAP expression in clear cell renal cell carcinoma (ccRCC) along with its clinical implication. METHODS: Using computational tools analysis of different freely accessible gene databases, the expression pattern, clinical importance, co-expressed genes, and signaling pathways of FAP in ccRCC were thoroughly investigated. FAP expression was examined in clinical ccRCC specimens through qRT-PCR, western blotting and immunohistochemistry. Furthermore, in vitro and in vivo experiments were carried out using flow cytometry, CCK-8, wound-healing and Transwell assays, as well as xenograft tumor model, respectively. RESULTS: FAP levels were found to be significantly elevated in ccRCC based on bioinformatic data from public databases. Patients who exhibited higher expression levels of FAP had poorer prognoses, according to Kaplan-Meier analysis of survival data. In addition, diagnostic and prognostic value of FAP in ccRCC was figured out by ROC curve and prognostic nomogram model. In vitro study revealed that the over-expression FAP accelerated cell proliferation, migration as well as invasion, and suppressed cell apoptosis, but silencing of FAP had the opposite effect. FAP suppression reduced the PI3K/AKT/mTOR pathway's stimulation, whereas FAP up-regulation increased the stimulation of the pathway. Blocking the PI3K/AKT/mTOR signaling pathway with the dual PI3K/mTOR inhibitor BEZ235 repressesed cancer-promoting effect of FAP. Additionally, we found that the downregulation of FAP was effective at slowing tumor progression in vivo. CONCLUSION: It is possible that FAP could be a reliable biomarker for the diagnosis and prognosis of ccRCC because of its role in the ccRCC progression via triggering the PI3K/AKT/mTOR signaling pathway.

GREM1 is a potential biomarker for the progression and prognosis of bladder cancer.

BACKGROUND: Gremlin-1 (GREM1) is a protein closely related to tumor growth, although its function in bladder cancer (BCa) is currently unknown. Our first objective was to study the GREM1 treatment potential in BCa. METHODS: BCa tissue samples were collected for the detection of GREM1 expression using Western blot analysis and Immunofluorescence staining. Association of GREM1 expression with clinicopathology and prognosis as detected by TCGA (The Cancer Genome Atlas) database. The functional investigation was tested by qRT-PCR, western blot analysis, CCK-8, cell apoptosis, wound healing, and transwell assays. The interaction between GREM1 and the downstream PI3K/AKT signaling pathway was assessed by Western blot analysis. RESULTS: GREM1 exhibited high expression in BCa tissues and was linked to poor prognosis. Stable knockdown of GREM1 significantly inhibited BCa cell (T24 and 5637) proliferation, apoptosis, migratory, invasive, as well as epithelial-mesenchymal transition (EMT) abilities. GREM1 promotes the progression in BCa via PI3K/AKT signaling pathway. CONCLUSION: Findings demonstrate that the progression-promoting effect of GREM1 in BCa, providing a novel biomarker for BCa-targeted therapy.

MiR-195-5p is involved in testicular ischemia/reperfusion injury by directly targeting PELP1 and regulating spermatogonia pyroptosis.

BACKGROUND AND OBJECTIVE: Ischemia/reperfusion injury (IRI), which is characterized by testicular torsion and causes permanent impairment of spermatogenic function, is linked with pyroptosis. Studies have implicated endogenous small non-coding RNAs in IRI development across various organs. In this study, we elucidated the mechanism underlying miR-195-5p's action in regulating pyroptosis in testicular IRI. METHODS: We established two models, namely a testicular torsion/ detorsion (T/D) mouse model and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated germ cell model. Hematoxylin and eosin staining was performed to evaluate the testicular ischemic injury. The expression of pyroptosis-related proteins and reactive oxygen species production in testis tissues were detected using Western blotting, quantitative real-time PCR, malondialdehyde and superoxide dismutase assay kits and immunohistochemistry. Cell viability and cytotoxicity were evaluated using CCK-8 and LDH assays, whereas expression patterns of inflammatory proteins were measured using ELISA, immunofluorescence, and western blot assays. miR-195-5p interaction with PELP1 was validated by conducting the luciferase enzyme reporter test. RESULTS: Pyroptosis-related proteins NLRP3, GSDMD, IL-1ß, and IL-18 were significantly upregulated following testicular IRI. A similar pattern was observed in the OGD/R model. miR-195-5p was significantly downregulated in mouse IRI testis tissue and OGD/R-treated GC-1 cells. Notably, miR-195-5p downregulation promoted whereas its upregulation attenuated pyroptosis in OGD/R-treated GC-1 cells. Furthermore, we found that PELP1 is a miR-195-5p target. miR-195-5p attenuated pyroptosis in GC-1 cells by inhibiting PELP1 expression during OGD/R, and this protective effect was blocked upon miR-195-5p downregulation. Collectively, these results indicated that miR-195-5p inhibits testicular IRI-induced pyroptosis by targeting PELP1, suggesting that it has the potential to serve as a novel target for the future development of therapies for testicular torsion.

A High-Reliability RF MEMS Metal-Contact Switch Based on Al-Sc Alloy.

This paper presents a new metal-contact RF MEMS switch based on an Al-Sc alloy. The use of an Al-Sc alloy is intended to replace the traditional Au-Au contact, which can greatly improve the hardness of the contact, and thus improve the reliability of the switch. The multi-layer stack structure is adopted to achieve the low switch line resistance and hard contact surface. The polyimide sacrificial layer process is developed and optimized, and the RF switches are fabricated and tested for pull-in voltage, S-parameters, and switching time. The switch shows high isolation of more than 24 dB and a low insertion loss of less than 0.9 dB in the frequency range of 0.1-6 GHz.

Overexpression of sirtuin 1 attenuates calcium oxalate-induced kidney injury by promoting macrophage polarization.

Sirtuin 1 (SIRT1) protein is involved in macrophage differentiation, while NOTCH signaling affects inflammation and macrophage polarization. Inflammation and macrophage infiltration are typical processes that accompany kidney stone formation. However, the role and mechanism of SIRT1 in renal tubular epithelial cell injury caused by calcium oxalate (CaOx) deposition and the relationship between SIRT1 and the NOTCH signaling pathway in this urological disorder are unclear. This study investigated whether SIRT1 promotes macrophage polarization to inhibit CaOx crystal deposition and reduce renal tubular epithelial cell injury. Public single-cell sequencing data, RT-qPCR, immunostaining approaches, and Western blotting showed decreased SIRT1 expression in macrophages treated with CaOx or exposed to kidney stones. Macrophages overexpressing SIRT1 differentiated towards the anti-inflammatory M2 phenotype, significantly inhibiting apoptosis and alleviating injury in the kidneys of mice with hyperoxaluria. Conversely, decreased SIRT1 expression in CaOx-treated macrophages triggered Notch signaling pathway activation, promoting macrophage polarization towards the pro-inflammatory M1 phenotype. Our results suggest that SIRT1 promotes macrophage polarization towards the M2 phenotype by repressing the NOTCH signaling pathway, which reduces CaOx crystal deposition, apoptosis, and damage in the kidney. Therefore, we propose SIRT1 as a potential target for preventing disease progression in patients with kidney stones.

Recent advances in differential expression analysis for single-cell RNA-seq and spatially resolved transcriptomic studies.

Differential expression (DE) analysis is a necessary step in the analysis of single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) data. Unlike traditional bulk RNA-seq, DE analysis for scRNA-seq or SRT data has unique characteristics that may contribute to the difficulty of detecting DE genes. However, the plethora of DE tools that work with various assumptions makes it difficult to choose an appropriate one. Furthermore, a comprehensive review on detecting DE genes for scRNA-seq data or SRT data from multi-condition, multi-sample experimental designs is lacking. To bridge such a gap, here, we first focus on the challenges of DE detection, then highlight potential opportunities that facilitate further progress in scRNA-seq or SRT analysis, and finally provide insights and guidance in selecting appropriate DE tools or developing new computational DE methods.

Emodin alleviates testicular ischemia-reperfusion injury through the inhibition of NLRP3-mediated pyroptosis.

Ischemia-reperfusion injury (IRI) is a major cause of injury after testicular torsion and can lead to permanent impairment of spermatogenesis. Emodin (6-methyl-1,3,8-trihydroxyanthraquinone) has potent anti-inflammatory effects and may be protective against IRI in various organs. Herein, we evaluated the effects of emodin on pyroptosis in spermatogenic cells and its role in the process of testicular IRI. A testicular torsion/detorsion (TTD) mouse model and an oxygen-glucose deprivation/reperfusion (OGD/R) germ cell model were established. Hematoxylin and eosin staining was performed to evaluate the testicular ischemic injury. The expression of pyroptosis-related proteins and reactive oxygen species production in testis tissues were detected using Western blotting, quantitative real-time PCR, malondialdehyde and superoxide dismutase assay kits and immunohistochemistry. Cell viability and cytotoxicity were evaluated using Cell Counting Kit-8 and lactate dehydrogenase assay kit. Enzyme-linked immunosorbent assay, immunofluorescence and immunoblotting were performed to assess inflammatory protein levels. The results revealed that pyroptosis and inflammation levels were upregulated after testicular IRI, and emodin inhibited inflammation and pyroptosis by acting on NOD-like receptor thermal protein domain-associated protein 3 (NLRP3). Emodin exerts protective effects on testicular IRI by acting on the NLRP3 signaling pathway and inhibiting IRI-mediated pyroptosis. Emodin treatment attenuated testicular IRI and inhibited pyroptosis. Inhibitory effects of emodin on pyroptosis were attributed to the inhibition of NLRP3 inflammasomes. Thus, emodin could be an alternative treatment for testicular IRI.

Effects of Mask Material on Lateral Undercut of Silicon Dry Etching.

The silicon etching process is a core component of production in the semiconductor industry. Undercut is a nonideal effect in silicon dry etching. A reduced undercut is desired when preparing structures that demand a good sidewall morphology, while an enlarged undercut is conducive to the fabrication of microstructure tips. Undercut is related to not only the production parameters but also the mask materials. In this study, five mask materials-Cr, Al, ITO, SiNx, and SiO2-are chosen to compare the undercut effect caused by the isotropic etching process and the Bosch process. In the Bosch process, the SiNx mask causes the largest undercut, and the SiO2 mask causes the smallest undercut. In the isotropic process, the results are reversed. The effect of charges in the mask layer is found to produce this result, and the effect of electrons accumulating during the process is found to be negligible. The undercut effect can be enhanced or suppressed by selecting appropriate mask materials, which is helpful in the MEMS process. Finally, using an Al mask, a tapered silicon tip with a top diameter of 119.3 nm is fabricated using the isotropic etching process.

Design and Fabrication of a Novel Poly-Si Microhotplate with Heat Compensation Structure.

I Microhotplates are critical devices in various MEMS sensors that could provide appropriate operating temperatures. In this paper, a novel design of poly-Si membrane microhotplates with a heat compensation structure was reported. The main objective of this work was to design and fabricate the poly-Si microhotplate, and the thermal and electrical performance of the microhotplates were also investigated. The poly-Si resistive heater was deposited by LPCVD, and phosphorous doping was applied by in situ doping process to reduce the resistance of poly-Si. In order to obtain a uniform temperature distribution, a series of S-shaped compensation structures were fabricated at the edge of the resistive heater. LPCVD SiNx layers deposited on both sides of poly-Si were used as both the mechanical supporting layer and the electrical isolation layer. The Pt electrode was fabricated on the top of the microhotplate for temperature detection. The area of the heating membrane was 1 mm × 1 mm. Various parameters of the different size devices were simulated and measured, including temperature distribution, power consumption, thermal expansion and response time. The simulation and electrical-thermal measurement results were reported. For microhotplates with a heat compensation structure, the membrane temperature reached 811.7 °C when the applied voltage was 5.5 V at a heating power of 148.3 mW. A 3.8 V DC voltage was applied to measure the temperature distribution; the maximum temperature was 397.6 °C, and the area where the temperature reached 90% covered about 73.8% when the applied voltage was 3.8 V at a heating power of 70.8 mW. The heating response time was 17 ms while the microhotplate was heated to 400 °C from room temperature, and the cooling response time was 32 ms while the device was recovered to room temperature. This microhotplate has many advantages, such as uniform temperature distribution, low power consumption and fast response, which are suitable for MEMS gas sensors, humidity sensors, gas flow sensors, etc.

A Novel Packaged Ultra-High Q Silicon MEMS Butterfly Vibratory Gyroscope.

A novel three-dimensional (3D) wafer-level sandwich packaging technology is here applied in the dual mass MEMS butterfly vibratory gyroscope (BFVG) to achieve ultra-high Q factor. A GIS (glass in silicon) composite substrate with glass as the main body and low-resistance silicon column as the vertical lead is processed by glass reflow technology, which effectively avoids air leakage caused by thermal stress mismatch. Sputter getter material is used on the glass cap to further improve the vacuum degree. The Silicon-On-Insulator (SOI) gyroscope structure is sandwiched between the composite substrate and glass cap to realize vertical electrical interconnection by high-vacuum anodic bonding. The Q factors of drive and sense modes in BFVG measured by the self-developed double closed-loop circuit system are significantly improved to 8.628 times and 2.779 times higher than those of the traditional ceramic shell package. The experimental results of the processed gyroscope also demonstrate a high resolution of 0.1°/s, the scale factor of 1.302 mV/(°/s), and nonlinearity of 558 ppm in the full-scale range of ±1800°/s. By calculating the Allen variance, we obtained the angular random walk (ARW) of 1.281°/√h and low bias instability (BI) of 9.789°/h. The process error makes the actual drive and sense frequency of the gyroscope deviate by 8.989% and 5.367% compared with the simulation.

Chemical constituents from mushroom Geoglossum fallax and their bioactive activities.

Chemical investigation on the fruiting bodies of the mushroom Geoglossum fallax led to the isolation of two carboxamides, geoglamides A and B (1 and 2), one meroterpenoid, geoglol A (3), together with seven known metabolites (4-10). Their structures were identified by spectroscopic analyses as well as ECD calculations. Compounds 1 and 2 are rare long chain fatty amides containing a 4-oxo-1,4-dihydropyridine moiety, while compound 3 is a rare C6-C5 type meroterpenoid. Compound 1 displayed cytotoxic activity against human MCF-7 cells with an IC50 value of 25.9 ± 0.51 µM. compounds 2 and 8 showed weak pancreatic lipase inhibition activity. To our best knowledge, this is the first report of the chemical constituents in the genera Geoglossum and their bioactive activity.

Correlation between Pulmonary Artery Pressure and Vortex Duration Determined by 4D Flow MRI in Main Pulmonary Artery in Patients with Suspicion of Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the causes of pulmonary hypertension (PH) and requires invasive measurement of the mean pulmonary artery pressure (mPAP) during right heart catheterisation (RHC) for the diagnosis. 4D flow MRI could provide non-invasive parameters to estimate the mPAP. Twenty-five patients with suspected CTEPH underwent cardiac MRI. Mean vortex duration (%), pulmonary distensibility, right ventricular volumes and function were measured using 4D flow MRI and cine sequences, and compared with the mPAP measured by RHC. The mPAP measured during RHC was 33 ± 16 mmHg (10−66 mmHg). PH (defined as mPAP > 20 mmHg) was present in 19 of 25 patients (76%). A vortical flow was observed in all but two patients (92%) on 4D flow images, and vortex duration showed good correlation with the mPAP (r = 0.805; p < 0.0001). Youden index analysis showed that a vortex duration of 8.6% of the cardiac cycle provided a 95% sensitivity and an 83% specificity to detect PH. Reliability for the measurement of vortex duration was excellent for both intra-observer ICC = 0.823 and inter-observer ICC = 0.788. Vortex duration could be a useful parameter to non-invasively estimate mPAP in patients with suspected CTEPH.

Carbon dots as a promising therapeutic approach for combating cancer.

With advances in nanotechnology and the development of emerging therapeutic modalities, a surge in research on the use of nanomedicines for biomedical applications has occurred over the past three decades. Carbon dots (CDs) are new members of carbon-based nanomaterials that can be used in cancer treatment to reduce side effects of drugs and improve treatment efficiency, offering new medical opportunities for further research. Urged as such, we are encouraged to classify CDs-based cancer treatments, including photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), chemotherapy (CT), and synergistic therapy. The advantages of these approaches are summarized, as well as ways to improve certain shortcomings. Meanwhile, this review highlights the feasible practice of CDs in cancer treatment, which is further developed and widely used in the biomedical field.

Oleuropein attenuates testicular ischemia-reperfusion by inhibiting apoptosis and inflammation.

BACKGROUND: Ischemia-reperfusion injury (IRI) is the key reason of injury after testicular torsion and may eventually lead to male infertility. Oleuropein, a natural antioxidant isolated from Olea europaea, has shown beneficial effects in different models of ischemia. We evaluated the effects of oleuropein on testicular IRI and explored the underlying protective mechanisms. METHODS: A mouse testicular torsion/detorsion (T/D) model and an oxygen-glucose deprivation/reperfusion (OGD/R) germ cell model were established and treated with oleuropein. H&E staining was used to evaluate testicular pathological changes. Apoptosis and apoptosis-associated protein levels in testis tissues were assessed by TUNEL staining, immunohistochemical staining and western blot. Apoptosis levels and apoptosis-associated protein levels in GC-1 were evaluated by flow cytometry, immunofluorescence and western blot. Oxidative stress levels were assessed by malondialdehyde (MDA) and superoxide dismutase (SOD) kits. Cell viability and inflammatory protein levels were evaluated by CCK-8 assay coupled with qRT-PCR. RESULTS: Relative to the control group, SOD activity was markedly suppressed, while MDA, Bax, Caspase-3, TNF-α as well as IL-1ß levels were significantly increased in the T/D model and OGD/R model. However, all of the aforementioned alterations were relieved by oleuropein treatment. CONCLUSION: Our findings indicate that oleuropein may be a promising treatment option to attenuate testicular IRI via its anti-oxidant, anti-inflammatory as well as anti-apoptotic properties.

A High-Performance MEMS Accelerometer with an Improved TGV Process of Low Cost.

High-performance MEMS accelerometers usually use a pendulum structure with a larger mass. Although the performance of the device is guaranteed, the manufacturing cost is high. This paper proposes a method of fabricating high-performance MEMS accelerometers with a TGV process, which can reduce the manufacturing cost and ensure the low-noise characteristics of the device. The TGV processing relies on laser drilling, the metal filling in the hole is based on the casting mold and CMP, and the packaging adopts the three-layer anodic bonding process. Moreover, for the first time, the casting mold process is introduced to the preparation of MEMS devices. In terms of structural design, the stopper uses distributed comb electrodes for overload displacement suppression, and the gas released by the packaging method provides excellent mechanical damping characteristics. The prepared accelerometer has an anti-overload capability of 10,000 g, the noise density is less than 0.001°/√Hz, and it has ultra-high performance in tilt measurement.

SpatialMap: Spatial Mapping of Unmeasured Gene Expression Profiles in Spatial Transcriptomic Data Using Generalized Linear Spatial Models.

Recent advances in various single-cell RNA sequencing (scRNA-seq) technologies have enabled profiling the gene expression level with the whole transcriptome at a single-cell resolution. However, it lacks the spatial context of tissues. The image-based transcriptomics in situ studies (e.g., MERFISH and seqFISH) maintain the cell spatial context at individual cell levels but can only measure a limited number of genes or transcripts (up to roughly 1,000 genes). Therefore, integrating scRNA-seq data and image-based transcriptomics data can potentially gain the complementary benefits of both. Here, we develop a computational method, SpatialMap, to bridge the gap, which primarily facilitates spatial mapping of unmeasured gene profiles in spatial transcriptomic data via integrating with scRNA-seq data from the same tissue. SpatialMap directly models the count nature of spatial gene expression data through generalized linear spatial models, which accounts for the spatial correlation among spatial locations using conditional autoregressive (CAR) prior. With a newly developed computationally efficient penalized quasi-likelihood (PQL)-based algorithm, SpatialMap can scale up to performing large-scale spatial mapping analysis. Finally, we applied the SpatialMap to four publicly available tissue-paired studies (i.e., scRNA-seq studies and image-based transcriptomics studies). The results demonstrate that the proposed method can accurately predict unmeasured gene expression profiles across various spatial and scRNA-seq dataset pairs of different species and technologies.

How curriculum delivery translates into entrepreneurial skills: The mediating role of knowledge of information and communication technology.

This research examines how curriculum delivery predicts entrepreneurial skills, with knowledge of information and communication technology (ICT) as a mediator. Curriculum delivery with the multiple dimensions of objectives, contents, teaching strategies, and feedback and assessment was used in this study, and a quantitative research design was adopted. A questionnaire survey was used to collect data from 482 students at six universities in Lahore, Pakistan, and the partial-least-squares structural equation model in SmartPLS 3.2 was used for data analysis. The results show that all dimensions of curriculum delivery (i) do not influence entrepreneurial skills and (ii) positively influence the knowledge of ICT. Also, in the indirect relationships, all dimensions of curriculum delivery (i.e., objectives, contents, teaching strategies, and feedback and assessment) are associated positively with ICT knowledge. Therefore, ICT knowledge plays a mediating role between curriculum delivery and entrepreneurial skills. The results also show that curriculum delivery for educational entrepreneurs is not working effectively and efficiently in Pakistani universities, and it is concluded that curriculum delivery and ICT knowledge boost entrepreneurial skills. Finally, the conclusions, limitations, and practical implications of this study are presented in detail.