Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

Generation and propagation properties of Bessel-Gaussian beams with a rotationally symmetric power-exponent-phase vortex.

In this paper, the generation and propagation properties of Bessel-Gaussian (BG) rotationally symmetric power-exponent-phase vortex beam (RSPEPVBs) were demonstrated and discussed. The results showed that the BG-RSPEPVBs can be directly generated based on the spatial light modulator, of which the phase singularities were verified by the interference patterns with the plane wave. It can be found that the intensity distributions of the BG-RSPEPVBs, with different topological charges (TCs) and power orders, were fan-shaped and polycyclic, which possessed the characteristics of BG beams and RSPEPVBs, simultaneously. Thus, the propagation invariance of the BG-RSPEPVBs is better than that of Laguerre-Gaussian RSPEPVBs and RSPEPVBs. Moreover, the focusing spot of the BG-RSPEPVBs would evolve into a bright ring with the same ring radius at the focal plane, which is independent of the TC and more suitable for the applications of optical coupling, optical communication, optical trapping, and so on.

Water and Salt Concentration-Dependent Electrochemical Performance of Hydrogel Electrolytes in Zinc-Ion Batteries.

Zinc-ion batteries (ZIBs) are promising energy storage devices with safe, nonflammable electrolytes and abundant, low-cost electrode materials. Their practical applications are hampered by various water-related undesirable reactions, such as the hydrogen evolution reaction (HER), corrosion of zinc metal, and water-induced decay of cathode materials. Polymer hydrogel electrolytes were used to control these reactions. However, salt, water, and polymeric backbones intervene in polymer hydrogels, and currently, there are no systematic studies on how salt and water concentrations synergistically affect polymer hydrogels' electrochemical performance. Here, we used an in situ polymerization method to synthesize polyacrylamide (PAM) hydrogels with varied Zn(ClO4)2 (0.5 to 2.0 mol kg-1) and water (40 to 90 wt %) concentrations. Their electrochemical performances in Zn||Ti half-cells, Zn||Zn symmetrical cells, and Zn||V2O5 full cells have been comprehensively evaluated. Although the ionic conductivity of electrolytes increases with the salt concentration, a high salt concentration of 2.0 mol kg-1 with more Zn2+ solvated H2O would induce more severe HER and Zn corrosion at the electrolyte/electrode interfaces. A narrow window of the water concentration at 70-80 wt % is optimal to balance needs for achieving a high ionic conductivity and restricting water-related undesirable reactions. The chemically more active water counts roughly 64.1-73.1 wt % of the total water in electrolytes. PAM hydrogel electrolyte with 1.0 mol kg-1 Zn(ClO4)2 and 80 wt % water enables 1200 h of stable cycling in a Zn||Zn symmetric cell and 99.24% of Coulombic efficiency in a Zn||Ti half-cell. Due to the water-induced decay of V2O5, the electrolyte with 70 wt % water delivers the best performance in a Zn||V2O5 full cell, which can retain 73.7% of its initial capacity after 400 charge/discharge cycles. Our results show that achieving precise control of salt and water concentrations of hydrogel electrolytes in their optimal windows to reduce the fraction of chemically more active water while retaining high ionic conductivity is essential to enabling high-performance ZIBs.

Influence of Lactose Supplementation on Regulation of Streptococcus thermophilus on Gut Microbiota.

It has been found that Streptococcus thermophilus (S. thermophilus) influenced the gut microbiota and host metabolism with strain specificity in C57BL/6J mice in the previous study, though it remains unclear whether lactose as a dietary factor associated with dairy consumption is involved as the mediator in the interaction. In the present study, integrated analysis of 16S rRNA gene sequencing and untargeted metabolomics by liquid chromatography-mass spectrometry of fecal samples in C57BL/6J mice was applied to evaluate the effect of lactose on the regulation of gut microbiota by two S. thermophilus strains (4M6 and DYNDL13-4). The results showed that the influence of lactose supplementation on gut microbiota induced by S. thermophilus ingestion was strain-specific. Although two S. thermophilus strains ingestion introduced similar perturbations in the fecal microbiota and gut microbial metabolism, the regulation of DYNDL13-4 on the gut microbiota and metabolism was more affected by lactose than 4M6. More specifically, lactose and 4M6 supplementation mainly enriched pathways of d-glutamine and d-glutamate metabolism, alanine, aspartate, and glutamate metabolism, and tryptophan and phenylalanine metabolism in the gut, whereas 4M6 only enriched tryptophan and phenylalanine metabolism. DYNDL13-4-L (DYNDL13-4 with lactose) had significant effects on sulfur, taurine, and hypotaurine metabolism in the gut and on phenylalanine, tyrosine, tryptophan biosynthesis, and linoleic acid metabolism in serum relative to the DYNDL13-4. Our study demonstrated the strain-specific effect of lactose and S. thermophilus supplementation on gut microbiota and host metabolism. However, considering the complexity of the gut microbiota, further research is necessary to provide insights to facilitate the design of personalized fermented milk products as a dietary therapeutic strategy for improving host health.

A novel CPT1A covalent inhibitor modulates fatty acid oxidation and CPT1A-VDAC1 axis with therapeutic potential for colorectal cancer.

Colorectal cancer (CRC) is a common and deadly disease of the digestive system, but its targeted therapy is hampered by the lack of reliable and specific biomarkers. Hence, discovering new therapeutic targets and agents for CRC is an urgent and challenging task. Here we report that carnitine palmitoyltransferase 1A (CPT1A), a mitochondrial enzyme that catalyzes fatty acid oxidation (FAO), is a potential target for CRC treatment. We show that CPT1A is overexpressed in CRC cells and that its inhibition by a secolignan-type compound, 2,6-dihydroxypeperomin B (DHP-B), isolated from the plant Peperomia dindygulensis, suppresses tumor cell growth and induces apoptosis. We demonstrate that DHP-B covalently binds to Cys96 of CPT1A, blocks FAO, and disrupts the mitochondrial CPT1A-VDAC1 interaction, leading to increased mitochondrial permeability and reduced oxygen consumption and energy metabolism in CRC cells. We also reveal that CPT1A expression correlates with the survival of tumor-bearing animals and that DHP-B exhibits anti-CRC activity in vitro and in vivo. Our study uncovers the molecular mechanism of DHP-B as a novel CPT1A inhibitor and provides a rationale for its preclinical development as well as a new strategy for CRC targeted therapy.

Spatial Distribution of Parvalbumin-Positive Fibers in the Mouse Brain and Their Alterations in Mouse Models of Temporal Lobe Epilepsy and Parkinson's Disease.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.

Role of nano-hydrogels coated exosomes in bone tissue repair.

With the development of nanotechnology, nanomaterials are widely applied in different areas. Some nanomaterials are designed to be biocompatible and can be used in the medical field, playing an important role in disease treatment. Exosomes are nanoscale vesicles with a diameter of 30-200 nm. Studies have shown that exosomes have the effect of angiogenesis, tissue (skin, tendon, cartilage, et al.) repair and reconstruction. Nano-hydrogels are hydrogels with a diameter of 200 nm or less and can be used as the carrier to transport the exosomes into the body. Some orthopedic diseases, such as bone defects and bone infections, are difficult to handle. The emergence of nano-hydrogels coated exosomes may provide a new idea to solve these problems, improving the prognosis of patients. This review summarizes the function of nano-hydrogels coated exosomes in bone tissue repair, intending to illustrate the potential use and application of nano-hydrogels coated exosomes in bone disease.

Greater trochanteric osteotomy and subtrochanteric osteotomy in primary/revision total hip arthroplasty.

Osteotomy of the femur is necessary in some cases of primary/revision total hip arthroplasty (THA) procedure. There are two mainly used femur osteotomy methods in THA: greater trochanteric osteotomy and subtrochanteric osteotomy. Greater trochanteric osteotomy can improve hip exposure, provide greater stability against dislocation and favorably influence the abductor moment arm. Whether in the primary or revision THA, greater trochanteric osteotomy has its unique position. Subtrochanteric osteotomy adjusts the degree of femoral de-rotation and corrects the leg length. It is widely used in hip preservation and arthroplasty surgery. All osteotomy methods have specific indications, while nonunion is the commonest complication. In this paper, we analyze the greater trochanteric osteotomy and the subtrochanteric osteotomy in primary/revision THA and summarize the characteristics of different osteotomy methods.

Alignment analysis of Brainlab knee 3 navigation-guided total knee arthroplasty using the adjusted mechanical method.

Purpose: With the application of navigation technology in Total Knee Arthroplasty (TKA), TKA procedures have become various. Studies have shown that navigation can improve the alignment of patients' lower limbs. To verify this conclusion, we collected the clinical data from patients who underwent Brainlab knee 3 navigation-guided TKA. Brainlab knee 3 is a completely new software that takes a different approach to address the current challenges of navigated TKA. During the procedure, we applied the Adjusted Mechanical Alignment (AMA) principle and took soft tissue balance as a priority. We aim to explore the patients' lower limb alignment changes who underwent the Brainlab knee 3 navigation-guided TKA using the AMA method. Methods: Fifty consecutive patients who underwent total knee arthroplasty using the Brainlab knee3 knee navigation system (Smith&Nephew) from January to August 2021 by the same doctor (Yunsu Chen) in the Department of Joint Surgery of the Shanghai Sixth People's Hospital were included. Hip-Knee-Ankle Angle (HKAA), anatomic Femur Tibia Angle (FTA), Lateral Distal Femoral Angle (LDFA), and medial proximal tibia angle (MPTA) were measured on preoperative and postoperative full-length lower-limbs x-ray films or weight-bearing anterior and lateral knee radiographs for observational and descriptive study. The preoperative and postoperative knee alignment changes were analyzed through paired t-test or nonparametric Wilcoxon test using SPSS 25.0 software. Results: Pre-operative and post-operative HKAA both obeyed normal distribution. The mean preoperative HKAA was 169.8° (154.9-178.7°) with a standard deviation of 5.41; the postoperative HKAA was 175.7° (168.4-180.0°) with a standard deviation of 2.81. Using the two-sample paired t-test to analyze, the result showed P = 0.000 < 0.05; a statistically significant difference exists. The preoperative and postoperative FTA obeyed normal distribution as well. The mean preoperative FTA was 174.7° (163.4-179.9°) with a standard deviation of 3.90; postoperative 175.6° (167.0-179.9°) with a standard deviation of 2.77. Using the two-sample paired t-test to analyze, the result showed P = 0.140 > 0.05, the difference was not statistically significant. The preoperative LDFA was normally distributed, while postoperative LDFA was not. The mean preoperative LDFA was 90.7° (83.5-99.6°) with a standard deviation of 3.83; the median of postoperative LDFA was 91.6° (86.0-103.2°) with an interquartile range of 2.93. Using the two-sample paired Wilcoxon test, the result showed P = 0.052 > 0.05; the difference was not statistically significant. Preoperative MPTA obeyed normal distribution, while postoperative MPTA did not. The mean preoperative MPTA was 83.5° (72.7-92.9°), with a standard deviation of 3.66; the median of postoperative MPTA was 89.3° (84.6-95.6°), with an interquartile range of 1.45. Using the two-sample paired Wilcoxon test, the result shows P = 0.000 < 0.05; a statistically significant difference exists. Conclusion: In our study, AMA alignment was applied in Brainlab Knee3 computer navigation-assisted total knee arthroplasty. The femoral and tibial osteotomy angles were minimally adjusted according to soft tissue situations to reduce soft tissue release. We found AMA alignment provides good control of knee alignment in the coronal plane of the lower limbs, which is a reliable technique.

Carbon/iron by-product from catalytic methane decomposition as recyclable Fenton catalyst for pollutant degradation.

Direct catalytic decomposition of methane (CDM) has been studied as a possible emission-free hydrogen production route for over 100 years. However, the high cost of catalyst regeneration limits its practical applications. Here, we demonstrate that the solid by-product from CDM using Fe ore catalysts comprising carbon nano onions encapsulated with magnetic Fe cores (Fe@C) can serve as efficient and recyclable Fenton catalysts for pollutant degradation. Fe@C/H2O2 has better performance than FeSO4/H2O2 at similar Fe concentrations and can be used to decompose various pollutants. Mechanistic studies reveal that graphitic carbon layers and encapsulated Fe0 contribute to their high catalytic activity. Further, Fe@C can be easily recovered from an aqueous solution and reused due to the encapsulated magnetic Fe particles. Over three reused cycles, Fe@C/H2O2 only yields 1/8 of Fe sludges compared to FeSO4/H2O2, significantly reducing Fe sludge treatment costs. Overall, Fe@C demonstrates excellent application potentials in water and wastewater treatment, making H2 production via CDM economically more viable.

[Application of sliding trochanteric osteotomy in total hip arthroplasty for Crowe type â £ developmental dysplasia of the hip].

OBJECTIVE: To investigate the effectiveness of sliding trochanteric osteotomy (STO) in total hip arthroplasty (THA) for Crowe type Ⅳ developmental dysplasia of the hip (DDH). METHODS: Between July 2016 and April 2021, 52 patients (57 hips) with Crowe type Ⅳ DDH who underwent primary THA were enrolled according to inclusion criteria. There were 5 males and 47 females with a median age of 51 years (range, 18-76 years). There were 47 cases of single hip and 5 cases of bilateral hips. The leg length discrepancy (LLD) was 50.50 (44.00, 55.00) mm, visual analogue scale (VAS) score was 8.0 (6.0, 9.0), and Harris score was 58.0±5.0 before operation. Trendelenburg sign was positive in 46 patients (46 hips). All patients underwent STO and THA using Wagner-cone stem. The operation time, intraoperative blood loss, blood transfusion volume, Trendelenburg sign, and related complications were observed. During follow-up, VAS and Harris scores were recorded to evaluate the hip pain and function. X-ray film was used to measure the LLD and observe the bone union situations. RESULTS: The operation time was 90-125 minutes (mean, 105 minutes). Introperative blood loss was 420-800 mL (mean, 640 mL). Ten patients underwent blood transfusion and the amount of allogeneic blood transfusion was 2-4 U (mean, 3 U). All incisions healed by first intention after operation. All patients were followed up 4-60 months (median, 24 months). At last follow-up, LLD was 6.00 (4.00, 7.75) mm, showing significant difference when compared with that before operation ( Z=-6.278, P=0.000). After operation, 51 hips (89.5%) achieved bone union at the osteotomy site, 4 hips (7.0%) had fibrous union, and 2 hips (3.5%) had nonunion. The healing time of osteotomy was 3-12 months, with an average of 6 months. At last follow-up, the VAS score was 3.0 (2.0, 5.0) and the Harris score was 85.0±6.0. The differences between pre- and post-operation were significant ( Z=-6.176, P=0.000; t=-25.285, P=0.000). Trendelenburg sign remained positive in 4 patients (4 hips) at last follow-up and the difference was significant when compared with preoperative ( χ 2=67.947, P=0.000). One patient had a medial femoral cortical fracture when Wagner-cone stem was implanted during operation, and 2 patients had early symptoms of sciatic nerve palsy after operation, and no other related complications occurred. CONCLUSION: For Crowe type Ⅳ DDH patients, STO applied in THA can reduce the resected bone mass, provide better exposure of hip as well as improve function of hip abductor muscle. Wagner-cone stem is recommended.

Loss of Knee Flexion and Femoral Rollback of the Medial-Pivot and Posterior-Stabilized Total Knee Arthroplasty During Early-Stance of Walking in Chinese Patients.

Background The medial-pivot (MP) prosthesis was developed to produce more physiological postoperative knee kinematics and better patient satisfaction than traditional prostheses, but outcomes are inconsistent in different studies of Caucasian patients. This study aimed to investigate the postoperative patient satisfaction and in vivo knee kinematics of the MP and posterior-stabilized (PS) prosthesis during gait activity in Chinese patients. Methods A retrospective analysis of 12 patients was received for this study in each MP group and PS group. Patient-reported satisfaction level and Forgotten Joint Score (FJS) were evaluated with questionnaires. A dual fluoroscopic imaging system was used to investigate in vivo knee kinematics of MP and PS total knee arthroplasty (TKA) during treadmill walking at a speed of 0.4 m/s. Results Comparable promising patient satisfaction and overall FJS (MP 60.7 ± 15.35 vs. PS 51.3 ± 17.62, p = 0.174) were found between the MP and PS groups. Peak flexion appeared at around 70% of gait cycle with values of 52.4 ± 7.4° for MP and 50.1 ± 3.6° for PS groups (no difference). Both groups maintained a stable position at the stance phase and began to translated anteriorly at toe-off with an amount of 4.5 ± 2.3 mm in the MP and 6.6 ± 2.7 mm in the PS (p = 0.08) group until late swing. The range of this external rotation motion was 5.9 ± 4.8 and 6.2 ± 4.1° (p = 0.79) for the MP and PS, respectively. Conclusion A similar knee kinematics pattern characterized by a loss of early-stance knee flexion and femoral rollback during walking was observed in the MP and PS TKAs. Our study confirmed similar effectiveness of MP TKA compared to PS TKA in Chinese patients, while the change of knee kinematics of both implants during slow walking should be noted.

Flexible Zinc-Ion Hybrid Fiber Capacitors with Ultrahigh Energy Density and Long Cycling Life for Wearable Electronics.

Emerging wearable electronics require flexible energy storage devices with high volumetric energy and power densities. Fiber-shaped capacitors (FCs) offer high power densities and excellent flexibility but low energy densities. Zn-ion capacitors have high energy density and other advantages, such as low cost, nontoxicity, reversible Faradaic reaction, and broad operating voltage windows. However, Zn-ion capacitors have not been applied in wearable electronics due to the use of liquid electrolytes. Here, the first quasisolid-state Zn-ion hybrid FC (ZnFC) based on three rationally designed components is demonstrated. First, hydrothermally assembled high surface area and conductive reduced graphene oxide/carbon nanotube composite fibers serve as capacitor-type positive electrodes. Second, graphite fibers coated with a uniform Zn layer work as battery-type negative electrodes. Third, a new neutral ZnSO4 -filled polyacrylic acid hydrogel act as the quasisolid-state electrolyte, which offers high ionic conductivity and excellent stretchability. The assembled ZnFC delivers a high energy density of 48.5 mWh cm-3 at a power density of 179.9 mW cm-3 . Further, Zn dendrite formation that commonly happens under high current density is efficiently suppressed on the fiber electrode, leading to superior cycling stability. Multiple ZnFCs are integrated as flexible energy storage units to power wearable devices under different deformation conditions.

Application of economic plant for remediation of cadmium contaminated soils: Three mulberry (Moms alba L.) varieties cultivated in two polluted fields.

In order to study the role of mulberry (Moms alba L) as an economic crop for remediation of cadmium (Cd) contaminated soil, the transport of Cd from mulberry to silkworm were investigated. Three varieties of mulberry (Yuesang-11, Nongsang-14, and Qiangsang-1) with three planting densities were cultivated in two heavy metal-contaminated fields named Dongkou in Shaoyang city and Linxiang in Yueyang city in Hunan province respectively. The both field soils were contaminated by heavy metals, especially by Cd. The potential risks of heavy metals in Linxiang's soil were higher than those in Dongkou's because of higher concentrations of Cd. Since the promotion of Cd concentrations in aerial parts (stem, branch and leaf) resulted from the increase of planting density, the method of high planting density is beneficial to improve the efficiency of the remediation of Cd contaminated soil. The percentages of average Cd contents of mulberry in Dongkou accounted for 44%, 20%, 18% and 16% in roots, stems, branches and leaves respectively, while the Cd contents were 38%, 27%, 19% and 16% distributed in roots, stems, branches and leaves respectively. Mulberry leaves from contaminated soils was applied in food source of silkworms in this study. Although there is Cd uptake occurred in silkworm growth and its products (cocoons and chrysalis), Cd contents in cocoons are lower than the national standard (100 µg*kg-1) for textile industry of China. Therefore, mulberry can be regarded as an economical crop to control soil contamination with Cd.