Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

Graphene/silicon heterojunction for reconfigurable phase-relevant activation function in coherent optical neural networks.

Optical neural networks (ONNs) herald a new era in information and communication technologies and have implemented various intelligent applications. In an ONN, the activation function (AF) is a crucial component determining the network performances and on-chip AF devices are still in development. Here, we first demonstrate on-chip reconfigurable AF devices with phase activation fulfilled by dual-functional graphene/silicon (Gra/Si) heterojunctions. With optical modulation and detection in one device, time delays are shorter, energy consumption is lower, reconfigurability is higher and the device footprint is smaller than other on-chip AF strategies. The experimental modulation voltage (power) of our Gra/Si heterojunction achieves as low as 1 V (0.5 mW), superior to many pure silicon counterparts. In the photodetection aspect, a high responsivity of over 200 mA/W is realized. Special nonlinear functions generated are fed into a complex-valued ONN to challenge handwritten letters and image recognition tasks, showing improved accuracy and potential of high-efficient, all-component-integration on-chip ONN. Our results offer new insights for on-chip ONN devices and pave the way to high-performance integrated optoelectronic computing circuits.

Molecular Evolution and Protein Structure Variation of Dkk Family.

Dkks have inhibitory effects on the Wnt signaling pathway, which is involved in the development of skin and its appendages and the regulation of hair growth. The nucleotide sequences were compared and analyzed to further investigate the relationship between the structure and function of the Dkk gene family and vertebrate epidermal hair. The analysis of the molecular evolution of the Dkk family revealed that the evolution rate of the genes changed significantly after speciation, with the Aves and Reptilia branches showing accelerated evolution. Additionally, positive selection was observed at specific sites. The tertiary structure of the protein was also predicted. The analysis of the functional divergence of the Dkk family revealed that the functional divergence coefficient of each gene was greater than 0, with most of the functional divergence sites were located in the Cys-2 domain and a few in the Cys-1 domain. This suggests that the amino acid and functional divergence sites may play a role in regulating the binding of the Dkk family to LRP5/6, and thus affect the inhibition of Wnt signaling, leading to different functions of Dkk1, Dkk2, and Dkk4 in the development of skin hair follicles. In addition, the Dkk families of Aves and Reptilia may have undergone adaptive evolution and functional divergence.

Reversible Thermally Driven Phase Change of Layered In2Se3 for Integrated Photonics.

Two-dimensional In2Se3, an unconventional phase-change material, has drawn considerable attention for polymorphic phase transitions and electronic device applications. However, its reversible thermally driven phase transitions and potential use in photonic devices have yet to be explored. In this study, we observe the thermally driven reversible phase transitions between α and ß' phases with the assistance of local strain from surface wrinkles and ripples, as well as reversible phase changes within the ß phase family. These transitions lead to changes in the refractive index and other optoelectronic properties with minimal optical loss at telecommunication bands, which are crucial in integrated photonic applications such as postfabrication phase trimming. Additionally, multilayer ß'-In2Se3 working as a transparent microheater proves to be a viable option for efficient thermo-optic modulation. This prototype design for layered In2Se3 offers immense potential for integrated photonics and paves the way for multilevel, nonvolatile optical memory applications.

Genomic adaptation to extreme climate conditions in beef cattle as a consequence of cross-breeding program.

BACKGROUND: Understanding the evolutionary forces related to climate changes that have been shaped genetic variation within species has long been a fundamental pursuit in biology. In this study, we generated whole-genome sequence (WGS) data from 65 cross-bred and 45 Mongolian cattle. Together with 62 whole-genome sequences from world-wide cattle populations, we estimated the genetic diversity and population genetic structure of cattle populations. In addition, we performed comparative population genomics analyses to explore the genetic basis underlying variation in the adaptation to cold climate and immune response in cross-bred cattle located in the cold region of China. To elucidate genomic signatures that underlie adaptation to cold climate, we performed three statistical measurements, fixation index (FST), log2 nucleotide diversity (θπ ratio) and cross population composite likelihood ratio (XP-CLR), and further investigated the results to identify genomic regions under selection for cold adaptation and immune response-related traits. RESULTS: By generating WGS data, we investigated the population genetic structure and phylogenetic relationship of studied cattle populations. The results revealed clustering of cattle groups in agreement with their geographic distribution. We detected noticeable genetic diversity between indigenous cattle ecotypes and commercial populations. Analysis of population structure demonstrated evidence of shared genetic ancestry between studied cross-bred population and both Red-Angus and Mongolian breeds. Among all studied cattle populations, the highest and lowest levels of linkage disequilibrium (LD) per Kb were detected in Holstein and Rashoki populations (ranged from ~ 0.54 to 0.73, respectively). Our search for potential genomic regions under selection in cross-bred cattle revealed several candidate genes related with immune response and cold shock protein on multiple chromosomes. We identified some adaptive introgression genes with greater than expected contributions from Mongolian ancestry into Molgolian x Red Angus composites such as TRPM8, NMUR1, PRKAA2, SMTNL2 and OXR1 that are involved in energy metabolism and metabolic homeostasis. In addition, we detected some candidate genes probably associated with immune response-related traits. CONCLUSION: The study identified candidate genes involved in responses to cold adaptation and immune response in cross-bred cattle, including new genes or gene pathways putatively involved in these adaptations. The identification of these genes may clarify the molecular basis underlying adaptation to extreme environmental climate and as such they might be used in cattle breeding programs to select more efficient breeds for cold climate regions.

Inner filter effect-based red-shift and fluorescence dual-sensor platforms with sulfur quantum dots for detection and bioimaging of alkaline phosphatase.

Alkaline phosphatase (ALP), one of the vital biomarkers in several diseases, plays a role in indicating disease presence or severity in early diagnosis. Here, a simple H2O2 assisted top-down method was used to synthesize sulfur quantum dots (SQDs) with excitation and emission at 355 nm and 440 nm. Adding ALP into p-nitrophenyl phosphate (p-NPP) and SQDs was found to exhibit a red shift in the emission wavelength and fluorescence intensity quenching of SQDs, respectively, allowing us to propose dual-sensor platforms of red shift of emission wavelength (RSEW) and fluorescence quenching of SQDs. These dual-sensor platforms were highly sensitive and selective in ALP detection, with a linear response to ALP in the concentration range of 0.25 to 100 U L-1 and detection limits of 0.08 and 0.10 U L-1, respectively. The absorption of p-NP at 400 nm showed a good overlap with the excitation and emission of SQDs, leading to inner filter effect-based RSEW and fluorescence quenching of SQDs. This sensor platform was successfully applied in ALP sensing of serum samples as well as monitoring of ALP in cells. More importantly, this platform can serve as an example of using RSEW to detect ALP.

Endoplasmic reticulum stress promoted acinar cell necroptosis in acute pancreatitis through cathepsinB-mediated AP-1 activation.

Acinar cell death and inflammatory response are two important events which determine the severity of acute pancreatitis (AP). Endoplasmic reticulum (ER) stress and necroptosis are involved in this process, but the relationships between them remain unknown. Here, we analyzed the interaction between ER stress and necroptosis and the underlying mechanisms during AP. Experimental pancreatitis was induced in Balb/C mice by caerulein (Cae) and lipopolysaccharide (LPS) or L-arginine (L-Arg) in vivo, and pancreatic acinar cells were also used to follow cellular mechanisms during cholecystokinin (CCK) stimulation in vitro. AP severity was assessed by serum amylase, lipase levels and histological examination. Changes in ER stress, trypsinogen activation and necroptosis levels were analyzed by western blotting, enzyme-linked immunosorbent assay (ELISA), adenosine triphosphate (ATP) analysis or lactate dehydrogenase (LDH) assay. The protein kinase C (PKC)α -mitogen-activated protein kinase (MAPK) -cJun pathway and cathepsin B (CTSB) activation were evaluated by western blotting. Activating protein 1 (AP-1) binding activity was detected by electrophoretic mobility shift assay (EMSA). We found that ER stress is initiated before necroptosis in CCK-stimulated acinar cells in vitro. Inhibition of ER stress by 4-phenylbutyrate (4-PBA) can significantly alleviate AP severity both in two AP models in vivo. 4-PBA markedly inhibited ER stress and necroptosis of pancreatic acinar cells both in vitro and in vivo. Mechanistically, we found that 4-PBA significantly reduced CTSB maturation and PKCα-JNK-cJun pathway -mediated AP-1 activation during AP. Besides, CTSB inhibitor CA074Me markedly blocked PKCα-JNK-cJun pathway -mediated AP-1 activation and necroptosis in AP. However, pharmacologic inhibition of trypsin activity with benzamidine hydrochloride had no effect on PKCα-JNK-cJun pathway and necroptosis in CCK-stimulated pancreatic acinar cells. Furthermore, SR11302, the inhibitor of AP-1, significantly lowered tumor necrosis factor (TNF) α levels, and its subsequent receptor interacting protein kinases (RIP)3 and phosphorylated mixed lineagekinase domain-like (pMLKL) levels, ATP depletion and LDH release rate in CCK-stimulated pancreatic acinar cells. To sum up, all the results indicated that during AP, ER stress promoted pancreatic acinar cell necroptosis through CTSB maturation, thus induced AP-1 activation and TNFα secretion via PKCα-JNK-cJun pathway, not related with trypsin activity. These findings provided potential therapeutic target and treatment strategies for AP or other cell death-related diseases.

Ionic-electronic Conductive Fabric Electrodes for Wearable Biopotential Monitoring.

This work proposed a low-cost and convenient way to develop textile electrodes with mixed conductive polymer by drop-casting. The effect of a conductivity enhancing agent (i.e., ethylene glycol (EG)) for PEDOT:PSS-coated fabric electrodes was investigated specifically. The results showed that the conductivity of the fabric electrode reached the highest with the addition of 20% EG compared to 0% and 5% EG loadings, which was different from that of thin-film electrodes in previous studies. In addition, the stability of the conductivity to washing was improved with the addition of the crosslinker GOPS and the surfactant DBSA. The signal quality in electrocardiogram recording with the PEDOT:PSS-coated fabric electrodes were comparable to that of commercial wet electrodes and outperformed silver-coated textile electrodes. Clinical Relevance- The dry textile electrodes with high conductivity and biopotential signal quality are of vital importance for wearable health monitoring to enable the early diagnosis and treatment of chronic diseases.

Development and validation of a cancer-associated fibroblast-derived lncRNA signature for predicting clinical outcomes in colorectal cancer.

Cancer-associated fibroblasts (CAFs) are actively involved in cancer progression through generating extracellular matrix and orchestrating the crosstalk within the tumor microenvironment (TME). This study aimed to develop and validate a CAF-derived lncRNA (long non-coding RNA) (CAFDL) signature for predicting clinical outcomes in colorectal cancer (CRC). Clinical data and transcriptomic profiles of 2,320 patients with CRC from The Cancer Genome Atlas (TCGA)-COAD and TCGA-READ datasets and 16 Gene Expression Omnibus datasets were included in this study. CAFDLs were identified using weighted gene co-expression network analysis. The CAFDL signature was constructed using the least absolute shrinkage and selection operator analysis in the TCGA-CRC training set. Multiple CRC cohorts and pan-cancer cohorts were used to validated the CAFDL signature. Patients with high CAFDL scores had significantly worse overall survival and disease-free survival than patients with low CAFDL scores in all CRC cohorts. In addition, non-responders to fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, and irinotecan (FOLFIRI) chemotherapy, chemoradiotherapy, bevacizumab, and immune checkpoint inhibitors had significantly higher CAFDL scores compared with responders. Pan-cancer analysis showed that CAFDL had prognostic predictive power in multiple cancers such as lung adenocarcinoma, breast invasive carcinoma, stomach adenocarcinoma, and thyroid carcinoma. The CAFDL signature was positively correlated with transforming growth factor-beta (TGF-ß) signaling, epithelial-mesenchymal transition, and angiogenesis pathways but negatively correlated with the expression of immune checkpoints such as PDCD1, CD274, and CTLA4. The CAFDL signature reflects CAF properties from a lncRNA perspective and effectively predicts clinical outcomes in CRC and across pan-cancer. The CAFDL signature can serve as a useful tool for risk stratification and provide new insights into the underlying mechanisms of CAFs in cancer immunity.

Waveguide-Integrated PdSe2 Photodetector over a Broad Infrared Wavelength Range.

Hybrid integration of van der Waals materials on a photonic platform enables diverse exploration of novel active functions and significant improvement in device performance for next-generation integrated photonic circuits, but developing waveguide-integrated photodetectors based on conventionally investigated transition metal dichalcogenide materials at the full optical telecommunication bands and mid-infrared range is still a challenge. Here, we integrate PdSe2 with silicon waveguide for on-chip photodetection with a high responsivity from 1260 to 1565 nm, a low noise-equivalent power of 4.0 pW·Hz-0.5, a 3-dB bandwidth of 1.5 GHz, and a measured data rate of 2.5 Gbit·s-1. The achieved PdSe2 photodetectors provide new insights to explore the integration of novel van der Waals materials with integrated photonic platforms and exhibit great potential for diverse applications over a broad infrared range of wavelengths, such as on-chip sensing and spectroscopy.

The impact of different feeds on DNA methylation, glycolysis/gluconeogenesis signaling pathway, and gene expression of sheep muscle.

DNA methylation is an important epigenetic regulatory form that regulates gene expression and tissue development. This study compared the effects of high fiber, low protein (HFLP) and low fiber, high protein (LFHP) diets on the DNA methylation profile of twin lambs' muscles, their effect on glycolysis/gluconeogenesis and related pathways by transcriptome and deep whole-genome bisulfite sequencing (WGBS). Results identified 1,945 differentially methylated regions (DMRs) and 1,471 differentially methylated genes (DMGs). Also, 487 differentially expressed transcripts belonging to 368 differentially expressed genes (DEGs) were discovered between the twin lambs under different diets. Eleven overlapped genes were detected between the DEGs and the DMGs. FKBP5 and FOXO1 were detected to be significantly different. The FOXO1 regulated cAMP and the glycolysis/gluconeogenesis pathways. The glycolysis/gluconeogenesis, and the FOXO pathways were significantly enriched. The expressions of HOMER1 and FOXO1 in the HFLP group were significantly higher than those in the LFHP group. There is a significant correlation between the upregulated gene expression and hypomethylation of HOMER1 and FOXO1 gene in HFLP group. The results showed that FOXO1 induces PDK4 expression in muscle while regulating FKBP5 activity, which stimulates glucose production by activating specific gluconeogenesis target genes. The FOXO1 was able to regulate the glucose metabolism, the cAMP and the occurrence of glycolysis/gluconeogenesis pathways. This study showed that feed type can affect the methylation levels of the glycolysis related gluconeogenesis genes and interaction pathways, providing new ideas for a better understanding of the regulation of muscle energy metabolism and feed development.

Immunologic Gene Sets Reveal Features of the Tumor Immune Microenvironment and Predict Prognosis and Immunotherapy Response: A Pan-Cancer Analysis.

In the treatment of cancer, anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immunotherapy has achieved unprecedented clinical success. However, the significant response to these therapies is limited to a small number of patients. This study aimed to predict immunotherapy response and prognosis using immunologic gene sets (IGSs). The enrichment scores of 4,872 IGSs in 348 patients with metastatic urothelial cancer treated with anti-PD-L1 therapy were computed using gene set variation analysis (GSVA). An IGS-based classification (IGSC) was constructed using a nonnegative matrix factorization (NMF) approach. An IGS-based risk prediction model (RPM) was developed using the least absolute shrinkage and selection operator (LASSO) method. The IMvigor210 cohort was divided into three distinct subtypes, among which subtype 2 had the best prognosis and the highest immunotherapy response rate. Subtype 2 also had significantly higher PD-L1 expression, a higher proportion of the immune-inflamed phenotype, and a higher tumor mutational burden (TMB). An RPM was constructed using four gene sets, and it could effectively predict prognosis and immunotherapy response in patients receiving anti-PD-L1 immunotherapy. Pan-cancer analyses also demonstrated that the RPM was capable of accurate risk stratification across multiple cancer types, and RPM score was significantly associated with TMB, microsatellite instability (MSI), CD8+ T-cell infiltration, and the expression of cytokines interferon-γ (IFN-γ), transforming growth factor-ß (TGF-ß) and tumor necrosis factor-α (TNF-α), which are key predictors of immunotherapy response. The IGSC strengthens our understanding of the diverse biological processes in tumor immune microenvironment, and the RPM can be a promising biomarker for predicting the prognosis and response in cancer immunotherapy.

Silicon Thermo-Optic Switches with Graphene Heaters Operating at Mid-Infrared Waveband.

The mid-infrared (MIR, 2-20 µm) waveband is of great interest for integrated photonics in many applications such as on-chip spectroscopic chemical sensing, and optical communication. Thermo-optic switches are essential to large-scale integrated photonic circuits at MIR wavebands. However, current technologies require a thick cladding layer, high driving voltages or may introduce high losses in MIR wavelengths, limiting the performance. This paper has demonstrated thermo-optic (TO) switches operating at 2 µm by integrating graphene onto silicon-on-insulator (SOI) structures. The remarkable thermal and optical properties of graphene make it an excellent heater material platform. The lower loss of graphene at MIR wavelength can reduce the required cladding thickness for the thermo-optics phase shifter from micrometers to tens of nanometers, resulting in a lower driving voltage and power consumption. The modulation efficiency of the microring resonator (MRR) switch was 0.11 nm/mW. The power consumption for 8-dB extinction ratio was 5.18 mW (0.8 V modulation voltage), and the rise/fall time was 3.72/3.96 µs. Furthermore, we demonstrated a 2 × 2 Mach-Zehnder interferometer (MZI) TO switch with a high extinction ratio of more than 27 dB and a switching rise/fall time of 4.92/4.97 µs. A comprehensive analysis of the device performance affected by the device structure and the graphene Fermi level was also performed. The theoretical figure of merit (2.644 mW-1µs-1) of graphene heaters is three orders of magnitude higher than that of metal heaters. Such results indicate graphene is an exceptional nanomaterial for future MIR optical interconnects.

[Development of Novel Guide Device for Cannulated Screws Implantation in Femoral Neck Fracture Surgery].

Cannulated Screw is a common internal fixation for the treatment of femoral neck fractures. However, the traditional implantation method has disadvantages such as inaccuracy and large radiation exposure. Based on the anatomical characteristics of the femoral neck and geometric principles, we develop a novel guide device for cannulated screws insertion. The cadaver experiment showed that it can improve the accuracy of cannulated screws implantation, reduce puncture attempts and the radiation exposure of doctors and patients.

The Dynamic Change of Gene-Regulated Networks in Cashmere Goat Skin with Seasonal Variation.

The Cashmere goat (Capra hircus) is renowned for its high-quality fiber production trait. The hair cycle in Cashmere goat has an annual rhythm. To deepen the understanding of the molecular foundation of annual rhythm in the skin of Cashmere goat, we did a comparative analysis of the Cashmere goat skin transcriptome all year round. 4002 Differentially expressed genes (DEGs) were identified with seasonal variations. 12 months transcriptome were divided into four developmental stages: Jan-Mar, Apr-Jul, Aug-Oct, and Nov-Dec based on gene expression patterns. 13 modules of highly correlated genes in skin were identified using WGCNA. Ten of these modules were consistent with the development stages. The gene function of those genes in each module was analyzed by functional enrichment. The results indicated that Wnt and Hedgehog signaling pathways were inhibited from January to March and activated from April to July. The cutaneous immune system of Cashmere goats has high activity from August to October. Fatty acid metabolism dominates goat skin from November to December. This study provides new information related to the annual skin development cycle, which could provide molecular biological significance for understanding the seasonal development and response to the annual rhythm of skin.

Severe Pneumonia Caused by Infection With Tropheryma whipplei Complicated With Acinetobacter baumannii Infection: A Case Report Involving a Young Woman.

Whipple's disease is a very rare systemic infectious disease, and very few cases have been reported. However, it can be fatal if not diagnosed and treated appropriately. The major clinical manifestations of this disease are usually digestive and nervous system symptoms. The majority of patients are male and between 40 and 50 years old. Although respiratory symptoms of this disease have rarely been reported, they pose a serious threat to the lives of the patients, especially when they progress to severe pneumonia. During admission to the hospital, Acinetobacter baumannii infection makes treatment more difficult. While most patients are middle-aged men, more attention should be given to the diagnosis and treatment of affected young women. To our knowledge, the case presented in the study is the first case of Tropheryma whipplei infection that resulted in severe pneumonia and was complicated by A. baumannii infection during treatment. We hope that our study can serve as a reference for the diagnosis and treatment of related cases in the future.

High-Performance Waveguide-Integrated Bi2O2Se Photodetector for Si Photonic Integrated Circuits.

Due to the excellent electrical and optical properties and their integration capability without lattice matching requirements, low-dimensional materials have received increasing attention in silicon photonic circuits. Bi2O2Se with high carrier mobility, narrow bandgap, and good air stability is very promising for high-performance near-infrared photodetectors. Here, the chemical vapor deposition method is applied to grow Bi2O2Se onto mica, and our developed polycarbonate/polydimethylsiloxane-assisted transfer method enables the clean and intact transfer of Bi2O2Se on top of a silicon waveguide. We demonstrated the Bi2O2Se/Si waveguide integrated photodetector with a small dark current of 72.9 nA, high responsivity of 3.5 A·W-1, fast rise/decay times of 22/78 ns, and low noise-equivalent power of 15.1 pW·Hz-0.5 at an applied voltage of 2 V in the O-band for transverse electric modes. Additionally, a microring resonator is designed for enhancing light-matter interaction, resulting in a wavelength-sensitive photodetector with reduced dark current (15.3 nA at 2 V) and more than a 3-fold enhancement in responsivity at the resonance wavelength, which is suitable for spectrally resolved applications. These results promote the integration of Bi2O2Se with a silicon photonic platform and are expected to accelerate the future use of integrated photodetectors in spectroscopy, sensing, and communication applications.