Identification of THSD7B and PRMT9 mutations as risk factors for familial lung adenocarcinoma: A case report.

RATIONALE: Lung tumors arise from the unrestrained malignant growth of pulmonary epithelial cells. Lung cancer cases include both small and non-small cell lung cancers, with lung adenocarcinoma (LUAD) accounting for roughly half of all non-small cell lung cancer cases. Research focused on familial cancers suggests that approximately 8% of lung cancer cases are linked to genetic susceptibility or heritability. The precise genetic factors that underlie the onset of lung cancer, however, remain to be firmly established. PATIENT CONCERNS: A 43-year-old presented with nodules in the lower left lung lobe. Following initial antibiotic treatment in a local hospital, these nodules remained present and the patient subsequently underwent the resection of the left lower lobe of the lung. The patient also had 4 family members with a history of LUAD. DIAGNOSIS: Immunohistochemical staining results including cytokeratin 7 (+), TTF-1 (+), new aspartic proteinase A (+), CK5/6 (-), P63 (-), and Ki-67 (5%+) were consistent with a diagnosis of LUAD. INTERVENTION: Whole exome sequencing analyses of 5 patients and 6 healthy family members were performed to explore potential mutations associated with familial LUAD. OUTCOMES: Whole exome sequencing was conducted, confirming that the proband and their 4 other family members with LUAD harbored heterozygous THSD7B (c.A4000G:p.S1334G) mutations and homozygous PRMT9 (c.G40T:p.G14C) mutations, as further confirmed via Sanger sequencing. These mutations were predicted to be deleterious using the SIFT, PolyPhen2, and MutationTaster algorithms. Protein structure analyses indicated that the mutation of the serine at amino acid position 1334 in THSD7B to a glycine would reduce the minimum free energy from 8.08 kcal/mol to 68.57 kcal/mol. The identified mutation in the PRMT9 mutation was not present in the predicted protein structure. I-Mutant2.0 predictions indicated that both of these mutations (THSD7B:p.S1334G and PRMT9: p.G14C) were predicted to reduce protein stability. LESSONS: Heterozygous THSD7B (c.A4000G:p.S1334G) and the homozygous PRMT9 (c.G40T:p.G14C) mutations were found to be linked to LUAD incidence in the analyzed family. Early analyses of these genetic loci and timely genetic counseling may provide benefits and aid in the early diagnosis of familial LUAD.

NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer.

Netrin-4 (NTN4), a member of neurite guidance factor family, can promote neurite growth and elongation. This study aims to investigate if NTN4 correlates with prognosis and immune infiltration in breast cancer. The prognostic landscape of NTN4 and its relationship with immune infiltration in breast cancer were deciphered with public databases and immunohistochemistry (IHC) in tissue samples. The expression profiling and prognostic value of NTN4 were explored using UALCAN, TIMER, Kaplan-Meier Plotter and Prognoscan databases. Based on TIMER, relationships of NTN4 expression with tumor immune invasion and immune cell surface markers were evaluated. Transcription and survival analyses of NTN4 in breast cancer were investigated with cBioPortal database. The STRING database was explored to identify molecular functions and signaling pathways downstream of NTN4. NTN4 expression was significantly lower in invasive breast carcinoma compared with adjacent non-malignant tissues. Promoter methylation of NTN4 exhibited different patterns in breast cancer. Low expression of NTN4 was associated with poorer survival. NTN4 was significantly positively related to infiltration of CD8+ T cells, macrophages and neutrophils, whereas significantly negatively related to B cells and tumor purity. Association patterns varied with different subtypes. Various associations between NTN4 levels and immune cell surface markers were revealed. Different subtypes of breast cancer carried different genetic alterations. Mechanistically, NTN4 was involved in mediating multiple biological processes including morphogenesis and migration.

Microencapsulation and nanowarming enables vitrification cryopreservation of mouse preantral follicles.

Preantral follicles are often used as models for cryopreservation and in vitro culture due to their easy availability. As a promising approach for mammalian fertility preservation, vitrification of preantral follicles requires high concentrations of highly toxic penetrating cryoprotective agents (up to 6 M). Here, we accomplish low-concentration-penetrating cryoprotective agent (1.5 M) vitrification of mouse preantral follicles encapsulated in hydrogel by nanowarming. We find that compared with conventional water bath warming, the viability of preantral follicles is increased by 33%. Moreover, the cavity formation rate of preantral follicles after in vitro culture is comparable to the control group without vitrification. Furthermore, the percentage of MII oocytes developed from the vitrified follicles, and the birth rate of offspring following in vitro fertilization and embryo transfer are also similar to the control group. Our results provide a step towards nontoxic vitrification by utilizing the synergistic cryoprotection effect of microencapsulation and nanowarming.

Non-synonymous alterations in AKR7A3 and ABCA6 correlate with bleeding in aged patients treated with rivaroxaban.

Rivaroxaban is an oral anticoagulant that inhibits thrombin and blocks coagulation cascade through directly inactivating factors Xa. Despite rivaroxaban is widely used for prevention and treatment of venous thrombosis, and its common adverse reactions have been reported, including abnormal coagulation, mucosal hemorrhage, hematuria, and intracranial hemorrhage. To explore potential drivers of individual differences in adverse reactions induced by rivaroxaban, we performed whole-exome sequencing and found that AKR7A3 rs1738023/rs1738025 and ABCA6 rs7212506 are susceptible sites for rivaroxaban-related bleeding in aged patients treated with rivaroxaban. Gene functional annotation and signaling pathway enrichment indicated that homozygous mutations in AKR7A3 and ABCA6 might alter normal rivaroxaban transport and metabolism, and lead to continuous accumulation of activated drugs and toxic substances in vivo. Our results suggested that interindividual differences in bleeding events induced by rivaroxaban may be potentially driven by genetic alterations related to abnormal metabolism and transport of rivaroxaban.

Progressive hemifacial atrophy in a Chinese patient: A case report.

BACKGROUND: Progressive hemifacial atrophy (PHA) is a rare and progressive condition of unknown etiology that is characterized by chronic progressive atrophy of the skin, subcutaneous tissue, muscle, and bone on 1 side of the face. However, its precise pathogenesis remains poorly understood. CASE PRESENTATION: Here, we report a case of PHA, which manifested as left-sided facial atrophy. Whole-exome sequencing of peripheral blood samples from the patient and his parents, together with bioinformatics analyses, led to the identification of mutations in ARHGAP4 and CFAP47. CONCLUSION: This report is the first to describe ARHGAP4 and CFAP47 mutations in a patient with PHA. These mutations may be related to the occurrence of hemifacial atrophy, although further studies are needed to clarify the role of ARHGAP4 and CFAP47 in the context of PHA pathogenesis.

Synergistic Ice Inhibition Effect Enhances Rapid Freezing Cryopreservation with Low Concentration of Cryoprotectants.

Despite recent advances in controlling ice formation and growth, it remains a challenge to design anti-icing materials in various fields from atmospheric to biological cryopreservation. Herein, tungsten diselenide (WSe2)-polyvinyl pyrrolidone (PVP) nanoparticles (NPs) are synthesized through one-step solvothermal route. The WSe2-PVP NPs show synergetic ice regulation ability both in the freezing and thawing processes. Molecularly speaking, PVP containing amides group can form hydrogen bonds with water molecules. At a macro level, the WSe2-PVP NPs show adsorption-inhibition and photothermal conversation effects to synergistically restrict ice growth. Meanwhile, WSe2-PVP NPs are for the first time used for the cryopreservation of human umbilical vein endothelial cell (HUVEC)-laden constructs based on rapid freezing with low concentrations of cryoprotectants (CPAs), the experimental results indicate that a minimal concentration (0.5 mg mL-1) of WSe2-PVP NPs can increase the viabilities of HUVECs in the constructs post cryopreservation (from 55.8% to 83.4%) and the cryopreserved constructs can also keep good condition in vivo within 7 days. Therefore, this work provides a novel strategy to synergistically suppress the formation and growth of the ice crystalsfor the cryopreservation of cells, tissues, or organs.

Vitrification of stem cell-laden core-shell microfibers with unusually low concentrations of cryoprotective agents.

Cell-laden alginate hydrogel microfibers are particularly useful for building and repairing complex tissues because they are long, thin, and flexible. Therefore, they have important application value in regenerative medicine and clinical treatments. Cryopreservation is indispensable in order to ensure their "off-the-shelf" ready availability. Ice-free vitrification is considered an ideal method to preserve stem cell constructs (from cells to the overall ultrastructure of hydrogel). However, the vitrification process for preserving cell constructs requires highly toxic and cell membrane permeable cryoprotective agents (pCPA) and even requires the assistance of complex physical field based space warming technology. Therefore, a simple and feasible method is urgently needed. In addition, there are no reports about microfiber vitrification, as reports are limited to microcapsules. In this study, a novel device with nylon mesh for vitreous cryopreservation of hydrogel microfibers is developed to achieve ultra-rapid heat transfer by effectively suppressing film boiling during cooling. This may provide a low-toxic and cost-effective method for vitrification of cell-laden hydrogel microfibers with ultra-low concentrations of pCPA, facilitating their application in regenerative medicine.

All-Aqueous-Phase Microfluidics for Cell Encapsulation.

Cell-laden hydrogel microcarriers are widely used in diverse biomedical applications like three-dimensional (3D) cell culture, cellular therapy, and tissue engineering, where microcarriers were generally produced by oil, which is the common but not optimal choice, as oil may cause cytotoxicity or protein denaturation. Here, an all-aqueous-phase microfluidics is presented to achieve oil-free emulsification of cell-laden microcapsules and 3D cell culture. Aqueous solutions with different concentration gradients are used as an immiscible continuous phase and a dispersed phase, and oscillation from a solenoid valve facilitates the formation of microcapsules at the water-water interface. By adjusting aqueous-phase flow rates and oscillating frequencies, core-shell microcapsules with controllable structures can be stably and continuously generated. In further 3D cell culture, encapsulated cells maintained good viabilities and aggregated together. These features show that the oil-free microfluidic method may have broad prospects in many biomedical applications.

A microfluidic platform with cell-scale precise temperature control for simultaneous investigation of the osmotic responses of multiple oocytes.

The temperature-dependent oocyte membrane permeability plays a significant role in oocyte cryopreservation, such as optimizing the addition/removal of cryoprotective agents and the rate of cooling/rewarming. However, the systems for studying the temperature dependence of oocyte membrane permeability are either too complicated or unable to achieve wide-range precise temperature control. In addition, these systems cannot achieve the simultaneous observation of multiple oocytes. Here, we report a novel microfluidic platform that combines a precise local temperature heater/detector and a simple global water bath to achieve wide-range accurate temperature control without increasing the difficulty of fabrication, and it also realizes non-interfering, position-controllable and non-missing capture of multiple oocytes for parallel experiments to increase throughput. The permeability coefficients (Lp, Ps) of the mouse oocyte membrane exposed to cryoprotective agents (1.5 M EG and 1.5 M PG) at four temperatures (4, 15, 25 and 37 °C) are consistent with those reported in previous works, which proves the feasibility and practicality of the microfluidic platform in this study.

Numerical experiments on evaporation and explosive boiling of ultra-thin liquid argon film on aluminum nanostructure substrate.

Evaporation and explosive boiling of ultra-thin liquid film are of great significant fundamental importance for both science and engineering applications. The evaporation and explosive boiling of ultra-thin liquid film absorbed on an aluminum nanostructure solid wall are investigated by means of molecular dynamics simulations. The simulated system consists of three regions: liquid argon, vapor argon, and an aluminum substrate decorated with nanostructures of different heights. Those simulations begin with an initial configuration for the complex liquid-vapor-solid system, followed by an equilibrating system at 90 K, and conclude with two different jump temperatures, including 150 and 310 K which are far beyond the critical temperature. The space and time dependences of temperature, pressure, density number, and net evaporation rate are monitored to investigate the phase transition process on a flat surface with and without nanostructures. The simulation results reveal that the nanostructures are of great help to raise the heat transfer efficiency and that evaporation rate increases with the nanostructures' height in a certain range.