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Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence is very limited, this study evaluated capmatinib-induced adverse events through data mining of the FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify the signals of capmatinib-related adverse events. The difference in capmatinib-associated adverse event signals was further investigated with respect to sex, age, weight, dose, onset time, continent, and concomitant drug. A total of 1518 reports and 4278 adverse events induced by capmatinib were identified. New significant adverse event signals emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, and oesophageal stenosis. Notably, higher risk of alanine aminotransferase and aspartate aminotransferase increases were observed in females, especially when capmatinib was combined with immune checkpoint inhibitors. Compared with Europeans and Asians, Americans were more likely to experience peripheral swelling, especially in people > 65 years of age. Renal impairment and increased blood creatinine were more likely to occur with single doses above 400 mg and in Asians. This study improves the understanding of safety profile of capmatinib. [ABSTRACT FROM AUTHOR]

Intestinal mucus is a complex natural hydrogel barrier with unique physical properties that impede the absorption of various oral drugs. Both washout from the upper water layer and the physical resistance of the mucus layer particularly affect bioavailability of, especially, highly water-soluble molecules. One potential strategy for designing pharmaceutical formulations is to add absorption enhancers (AEs). However, there are few reports of AEs that work on mucus and their underlying mechanisms, leading to imprecise application. In this study, we investigated chitooligosaccharide (COS) as a safe, low-cost, and effective oral drug AE. We revealed the hydrodynamic law of interaction between COS and the intestinal mucus layer, which was associated with absorption benefiting mucus structural reconstruction. Based on this, we designed a translational strategy to improve the bioavailability of a group of soluble oral drugs by drinking COS solution before administration. Moreover, this research is expected to expand its application scenario by reducing drug dosage such as avoiding gastro-intestinal irritation and slowing veterinary antibiotic resistance. Schematic illustration of COS pro-absorptive action mechanisms and its rational use. Firstly, the oral COS solution interacts with the intestinal mucus. Over time, COS can reconstruct the physical properties of the mucus layer. In addition, COS's intrinsic amino cation interacts electrostatically with MUC-2, changing the local viscosity of the mucus. This mode creates a favorable environment for hydrophilic drug molecules to pass through the mucus barrier when oral high water-soluble drugs can be better absorbed and oral bioavailability is improved. [Display omitted] • Chitooligosaccharide (COS) can reconstitute the drug absorption relevant intestinal mucus structure, including thickness, pore space, viscosity, etc. • The hydrodynamic model reveals the pro-absorption mechanism of COS and simulates the process of drug absorption. • This pro-absorption strategy can especially enhance the oral absorption of water-soluble drugs, potentially reduce toxicity and increase efficacy. [ABSTRACT FROM AUTHOR]

In this paper, we develop an efficient Boltzmann-equation-based mesoscopic approach to simulate three-dimensional (3D) compressible turbulence, using reduced Gauss–Hermite quadrature (GHQ) orders by redefining the second distribution in terms of the total energy in the double distribution function approach. This allows the use of two sets of 3D off-lattice discrete particle velocity models, namely, a 27 discrete velocity model of the seventh-order GHQ accuracy (D3V27A7) combined with a 13 discrete velocity model of the fifth-order GHQ accuracy (D3V13A5), to achieve full consistency with the Navier–Stokes–Fourier system. The source terms in the Boltzmann–Bhatnagar–Gross–Krook system are designed to adjust both the Prandtl number and bulk-to-shear viscosity ratio. Compressible decaying homogeneous isotropic turbulence (DHIT) is simulated at low and moderate turbulent Mach numbers to validate our code. It is observed that the simulation results are in good agreement with those in the existing literatures. Furthermore, the terms in the transport equation of turbulent kinetic energy are analyzed in detail, to illustrate four different transient stages from the initial random flow field to the developed DHIT. It is shown that the transient pressure-dilatation transfer happens rapidly, while the small-scale vortical structures take a longer time to establish physically. Compared to the existing literatures, our approach represents the most efficient mesoscopic scheme for compressible turbulence under the double distribution function formulation. [ABSTRACT FROM AUTHOR]

Antimony sulfide (Sb2S3) as a binary chalcogenide has emerged as a promising candidate for next-generation thin-film photovoltaics. Although breakthroughs have been made in terms of device performance in recent years, the power conversion efficiency is still far from the Shockley–Queisser limit. It is mainly attributed to the poor charge transport and abundant defects, which deteriorate the fill factor and result in grievous open-circuit voltage loss. Here, we improved the device performance through a synergetic approach: (i) by introducing ZnSnO3 as the second electron transport layer, the current leakage was effectively reduced, and the charge extraction was enhanced; then, (ii) the prepared Sb2S3 films were treated via a low-temperature and short-time post-treatment with thiourea, which significantly suppressed the carrier recombination and increased the open-circuit voltage. More importantly, we systematically analyzed the trap features of the Sb2S3 films with/without treatment, mainly including the trap density, trap level, and trap capture cross section. We found that defects near the surface due to elemental inhomogeneity by the hydrothermal method could be effectively passivated, and defect-assisted recombination was suppressed after the thiourea treatment. [ABSTRACT FROM AUTHOR]

• Based on the liquid diffusion of POMs and BC and high temperature carbonization strategy, 3D porous conductive network structure of carbon fiber based nanocomposites were prepared. • By changing the element type, drying mode and filling amount, the tuning of electromagnetic parameters and absorbing properties can be achieved. • The best synthesized sample 20 %-CS1 has excellent EMW absorption properties, with a maximum R L of −68.1 dB at 2.6 mm matching thickness and the EAB is 7.2 GHz. In order to enhance the wave-absorbing performance of dielectric/carbon fiber based wave-absorbing materials and explore the dissipative mechanism of electromagnetic wave (EMW), this study utilizes liquid diffusion of K 4 PW 11 O 39 Fe(III)(H 2 O) (α-PW 11 Fe), K 5 PW 11 O 39 Co(II)(H 2 O) (α-PW 11 Co), K 5 PW 11 O 39 Ni(II)(H 2 O) (α-PW 11 Ni) and bacterial cellulose (BC), as well as high temperature carbonization strategy to prepare polycrystalline polyphase transition metals and their compounds with three dimensional porous conductive network structure loaded carbon fiber based nanocomposites wave-absorbing materials. By changing the element type, drying mode and filling amount, we can achieve the tunability of electromagnetic parameters and absorbing properties. Impressively, the best synthesized sample 20 %-α-PW 11 Ni/BC derived carbon fiber based nanocomposites has excellent EMW absorption properties, with a maximum reflection loss (R L) of -68.1 dB at 2.6 mm matching thickness. The effective absorbing bandwidth (EAB) is 7.2 GHz, and the R L less than -10 dB in the frequency band of 2.2–5.0 mm thickness is 5.3 to 18.0 GHz. The excellent absorbing performance is attributed to the synergy of polarization and conductance, balanced impedance matching, good interface/dipole polarization, and multiple reflections and scattering. Therefore, the prepared composite has a broad application prospect in the field of EMW absorption, and provides a new idea for the design of new efficient absorbing materials. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Small subchromosomal deletions and duplications caused by copy number variants (CNVs) can now be detected with noninvasive prenatal testing (NIPT) technology. However, the clinical utility and validity of this screening for CNVs are still unknown. Here, we discuss some special conditions in which both cases simultaneously exhibited false positives caused by maternal CNVs and false negatives due to limitations of the technology. Case presentation: In case 1, NIPT indicated a 1.1 Mb deletion at 21q21.1, but the umbilical cord for array CGH (aCGH) revealed a 422 kb deletion at 15q13.3. Peripheral blood of the parents for aCGH showed a 1.1 Mb deletion at 21q21.1 in the mother's sample, and the same deletion at 15q13.3 was detected in the father's blood. In case 2, NIPT showed a 1.5 Mb deletion at 22q11.21, but aCGH of amniocytes revealed a 1.377 Mb duplication rather than a 1.5 Mb deletion at 22q11.21. Furthermore, aCGH analysis of the parental blood revealed a 647 kb deletion at 22q11.21 in the mother and a 2.8 Mb duplication of 22q11.21 in the father. Conclusions: Our findings not only highlight the significance of diagnostic testing following a positive cfDNA sequencing result but also the necessity for additional analytical and clinical validation before routine use in practice. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • An organic resistive switching memory device based on lotus leaves was prepared. • The device exhibits a resistive switching memory behavior with large resistance ratio. • The retention test of our device shows a more stable trend over long time. • This work indicates the lotus leaves hold potential application in electronic devices. Abstract The resistance random access memory (RRAM) based on biomaterials, which has the advantages of sustainable, green and environment-friendly, has great potential application in the sustainable electronic devices. Herein, lotus leaves, a very common aquatic herb serve as a dielectric layer, was used to prepare an organic resistive switching memory device with Ag/Lotus leaves/ITO structure for the first time. The biodegradable electronic device demonstrates a nonvolatile resistive switching memory behavior with large resistance ratio and long switching endurance at room temperature. This work exhibits the application prospect of the biomaterials in electronics with the biodegradability and biocompatibility, which provide an effective supplement to the research of organic bio-RRAM. [ABSTRACT FROM AUTHOR]

Background: Trichomonas vaginalis is a protozoan parasite, widely recognized as the most prevalent non-viral sexually transmitted infection (STI) globally. This infection is linked to various complications, including pelvic inflammatory disease, adverse pregnancy outcomes, and an increased risk of acquiring HIV. Current molecular detection methods for T. vaginalis are often costly and technically challenging. Methods: We developed a novel detection method for T. vaginalis using a multi-enzyme isothermal rapid amplification–clustered regularly interspaced short palindromic repeats (MIRA-CRISPR)/Cas13a-lateral flow device (LFD). This assay targets the repeated DNA sequence (GenBank: L23861.1) of T. vaginalis and is performed at a constant temperature of 37 °C for approximately 1 hour. Results: The detection limit of genomic DNA (gDNA) using our protocol was 1 × 10–4 ng/μl. Specificity was confirmed by the absence of cross-reaction with gDNA from various other microorganisms such as Staphylococcus aureus, Lactobacillus taiwanensis, Escherichia coli, Monilia albicans, Giardia lamblia, or Toxoplasma gondii. Among 30 clinical samples tested, the positive rates of T. vaginalis detection were 33.33% (10/30) by wet mount microscopy, 40% (12/30) by nested polymerase chain reaction (PCR), 40% (12/30) by MIRA-CRISPR/Cas13a-LFD, and 40% (12/30) by the culture method. Compared with the culture method, the gold standard for diagnosing trichomoniasis, wet mount microscopy showed a sensitivity of 83.3% and moderate diagnostic agreement (kappa value = 0.87). Both nested PCR and MIRA-CRISPR/Cas13a-LFD exhibited 100% sensitivity and excellent diagnostic agreement (kappa value = 1). Conclusions: The MIRA-CRISPR/Cas13a-LFD method is a convenient, rapid, stable, and accurate diagnostic tool for detecting T. vaginalis. This method has the potential to enhance the diagnosis and management of vaginitis, offering a significant improvement over existing diagnostic techniques. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) have been worldwide used as flame retardants. Among them, decabromodiphenyl ether (BDE-209) is the most applied and becomes ubiquitous in the environment and organisms. It can alter spontaneous behavior and affect the cholinergic system in rodents. Ultrasonic vocalizations (USVs) emitted by rat pups during isolation are widely employed as neurobehavioral indexes, and the cholinergic system supports their normal expression. However, whether BDE-209 can alter isolation USVs were unknown. In this study, BDE-209 was daily administered to mothers at 0, 500, or 1000 mg/kg b.w. from gestational day (GD) 15 to postnatal day (PND) 21. On PNDs 7, 10, 13, and 16, rat pups were individually isolated from mothers, and their USVs were recorded for 5 min after 5-min habituation and then analyzed. The results indicated that BDE-209 exposure can cause acoustic alterations in isolation USVs. The high-dose pups emitted USVs with shorter duration than the control pups did. Moreover, the percentages of frequency-modulated (FM) USVs in the high-dose pups were lower than those in the control pups. The mechanisms to alter acoustic characteristics of isolation USVs need further investigation. USV analysis is a useful method that provides neurobehavioral evidence. • BDE-209 exposure during GD 15-PND 21 causes acoustic alterations in isolation USVs. • High-dose pups exhibit USVs with shorter duration. • High-dose pups show lower percentages of frequency-modulated (FM) USVs. [ABSTRACT FROM AUTHOR]

Dengue hemorrhagic fever (DHF)/Dengue shock syndrome (DSS) is a fatal infectious disease that demands an effective treatment. Interferon (IFN)-stimulated genes (ISGs) induced by dengue virus (DENV) exert antiviral effects. Among ISGs, IFN-α inducible gene 6 (IFI6) was increased in DENV infected human umbilical vascular endothelial cells (HUVECs) by microarray analysis in our previous study. However, its function is incompletely understood. In this study, we confirmed that IFI6 was markedly induced in DENV infection of both primary HUVECs and EA.hy926 cell lines. Recombinant EA.hy926 cell lines in which IFI6 was either over-expressed (IFI6+/+) or knocked-down (IFI6-/-) were generated. The activation of caspase-3 and intrinsic apoptosis-related protein caspase-9 were down-regulated in IFI6+/+ but up-regulated in IFI6-/- cells at 24–48 hrs post-infection. After incubation with DENV for 48 hrs, the mitochondrial membrane potential (Δψ(m)) was more stable in IFI6+/+ cells but reduced in IFI6-/- cells, as assayed by fluorescence staining with JC-1. We observed that Bcl-2 expression was increased in IFI6+/+ and decreased in IFI6-/- cells. By contrast, Bax expression was decreased in IFI6+/+ and increased in IFI6-/- cells. It is presumed that the anti-apoptotic function of IFI6 is expressed by regulating the rheostatic balance between bcl-2/bax expression and inhibition of Δψ(m) depolarization during DENV infection of vascular endothelial cells(VECs). In addition, the pro-apoptotic protein X-linked Inhibitor of Apoptosis (XIAP)-Associated Factor 1(XAF1) expression had been reported to be up-regulated and led to the induction of apoptosis in DENV2-infected VECs,but the relationship between XAF1 and IFI6 dengue virus-induced apoptosis in VECs warrants further study. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and post-stroke cognitive impairment (PSCI) are the leading causes of progressive dementia related to neurodegenerative and cerebrovascular injuries in elderly populations. Despite decades of research, patients with these conditions still lack minimally invasive, low-cost, and effective diagnostic and treatment methods. MicroRNAs (miRNAs) play a vital role in AD and PSCI pathology. As they are easily obtained from patients, miRNAs are promising candidates for the diagnosis and treatment of these two disorders. In this study, we performed complete sequencing analysis of miRNAs from 24 participants, split evenly into the PSCI, post-stroke non-cognitive impairment (PSNCI), AD, and normal control (NC) groups. To screen for differentially expressed miRNAs (DE-miRNAs) in patients, we predicted their target genes using bioinformatics analysis. Our analyses identified miRNAs that can distinguish between the investigated disorders; several of them were novel and never previously reported. Their target genes play key roles in multiple signaling pathways that have potential to be modified as a clinical treatment. In conclusion, our study demonstrates the potential of miRNAs and their key target genes in disease management. Further in-depth investigations with larger sample sizes will contribute to the development of precise treatments for AD and PSCI. [ABSTRACT FROM AUTHOR]

Background: Cell-free fetal DNA in maternal plasma represents a source of fetal genetic material that can be sampled noninvasively. There are ample studies confirming the accuracy of NIPT in singleton pregnancies, but there is still relatively little studies demonstrate the feasibility and clinical application of a NIPT for fetal aneuploidy screening in twin pregnancies. Results: In this study, we have finished 432 twin pregnancies screening by NIPT. There were 4 double chorionic dichorionic diamniotic (DCDA) cases of true positive NIPT results, including 1of T18 and 3 of T21, and 1 monochorionic diamniotic (MCDA) cases of true positive NIPT results, including 1of T21. The combined false-positive frequency for trisomies 21, 18 was 0%. Furthermore, there were 2 cases of false positive NIPT results, including 1 of T7 and 1 of sex chromosome aneuploidy. There was no false negative case, which gave a combined sensitivity and specificity of 100 and 99.53% respectively. Conclusion: Our study demonstrated NIPT performed well in the detection of trisomy 21 in twin pregnancy. It is feasible and clinical applicable of NIPT for fetal aneuploidy screening in twin pregnancies. But, it needs a large number of clinical samples to demonstrate the applicability of other chromosomal abnormalities besides trisomies 21 and 18 in both singleton pregnancies and twin pregnancies. [ABSTRACT FROM AUTHOR]

Photomultiplication-type organic photodetectors have emerged as a class of next generation solution-processed photodetectors with high gain. Despite this promising feature, the reported photodectors still suffer from relatively large dark currents at high bias voltages. To overcome this drawback, a mechanistic understanding of the photomultiplication effect in organic photodiodes is required. In this work, we advanced the performance of photomultiplication-type organic photodetectors by tuning the active layer composition and interfacial layers. The optimized devices exhibit small dark currents and flat dark current–voltage curves under the reverse bias condition up to −10 V. The optimized photodetectors also reached an ultra-high responsivity of 23.6 A/W and the specific detectivity of 1.04 × 1012 Jones at −10 V. More importantly, we investigated the photomultiplication process with multiple transient techniques and revealed that the photoconductive gain effect is a slow process, which relies on the photo-Schottky effect enabled by charge carrier tunneling and the accumulation of holes. Furthermore, we also demonstrated prototypical pulsed-light detection based on the optimized devices, which showed great potential for real applications. [ABSTRACT FROM AUTHOR]

To date, whether ascending aorta dilation (AAD) should be considered a contraindication for transcatheter aortic valve replacement (TAVR) remains a topic of debate.. The study investigated the clinical outcome of TAVR in patients with bicuspid aortic valve stenosis (BAV-AS) complicated by AAD. We included patients with BAV-AS who underwent TAVR between 2012 and 2019. We collected patient perioperative clinical data., tracked clinical outcomes for over four years post-TAVR, and obtained echocardiography images one year postoperatively. The Kaplan-Meier method was employed for analyzing both unadjusted and adjusted survival data, which was compared using the log-rank test. COX regression and nomograms were used to assess the impact of AAD on post-TAVR clinical outcomes in patients with aortic stenosis (AS), with all-cause mortality as the primary clinical endpoint. A total of 111 BAV patients were included in this study. Long-term follow-up showed an increased mortality risk in patients with BAV-AAD (adjusted Kaplan–Meier analysis: P =.02/0.001). Cox correlation analysis indicated that age (OR = 1.137; P =.034), AAD (OR = 3.51; P =.038), and postoperative left ventricular pressure (LVSP) (OR: 0.959; P =.044) were predictive factors for mortality more than four years after TAVR in patients with BAV. The area under the curve of the Nomogram predicting long-term survival for the training set of patients based on the above metrics was 0.845 (95% CI: 0.696–0.994). Short-term cardiac ultrasound follow-up showed a more rapid rate of AA expansion (0.29 [0–0.34] vs. -1 [−3.3–1] mm/month, P =.001) and a smaller proportion of AA diameter reduction (7.1% vs. 53.7%, P =.001) in patients who died. Patients with BAV-AAD-AS treated with TAVR have an increased risk of long-term mortality, and clinical prediction models, including AAD age and postoperative LVSP, may predict long-term patient survival. The study investigated the clinical outcome of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (BAV-AS) complicated by ascending aorta dilation (AAD). Patients with BAV-AAD-AS treated with TAVR have an increased risk of long-term mortality. AAD, age and postoperative LVSP, may predict long-term patient survival. Short-term cardiac ultrasound follow-up showed a more rapid rate of AA expansion and a smaller proportion of AA diameter reduction in patients who died. A high postoperative AAD expansion rate may indicate an adverse clinical outcome. Surgery regimens for tolerable BAV-AADs and can be considered as a treatment option. [ABSTRACT FROM AUTHOR]

[Display omitted] • Quercetin-loaded PEGylated rapamycin micelles (QPRM) are designed. • Rapamycin exhibited unexpected disadvantage in cancer therapy and induced metastasis, which is reversed by quercetin. • QPRM show excellent angiogenesis and metastasis inhibition. • Rapamycin and quercetin combination shows synergistic anticancer effect. Cancer continues to be a significant health hazard to the patient's body around the globe, with more than 19 million incidents in 2020 worldwide, according to the world health organization, and it is expected to surpass 30 million in 2040. The advancement of nanomedicine focuses on enhancing the anticancer drugs that suffer from poor water solubility, unspecific cytotoxicity, and unfavorable pharmacokinetic properties. The most promising nanocarriers would be biodegradable and biocompatible, making the anticancer drugs soluble, preventing their aggregation, and enabling site-specific targeting. Herein, we formulated a rational design of two anticancer drugs (PEGylated rapamycin and quercetin) in a single micellar nanosystem, the ideal nanocarrier for water-insoluble drugs. After encapsulation, cytotoxicity and cellular uptake were increased. The quercetin loaded PEGylated rapamycin micelles (QRPM) exhibited significantly higher in vitro cytotoxicity in breast cancer cells than free drugs, mainly because of higher cellular uptake achieved via micelles. Moreover, the pharmacodynamic investigations indicated that QRPM significantly inhibited tumor growth compared to free drugs and PEGylated rapamycin micelles. Generally, QRPM could dramatically enhance the antitumor activity. They might be a promising drug delivery platform for anti-angiogenesis, -migration, and -invasion therapy as the nanosystem dramatically inhibited them compared with free drugs. [ABSTRACT FROM AUTHOR]

Smart agronomic management practices (e.g., employing lodging-resistant cultivars, appropriate fertilization, and applying plant growth regulators (PGRs)) can reduce crop lodging risk. However, their integrated effects on grain yield and lodging risk in rice paddies remain poorly defined. Here, we conducted a meta-analysis to examine the effects of agronomic practices on rice yield and lodging risk, synthesizing data from 68 published studies with 475 observations. Our results showed that compared with inbred varieties, hybrid rice increased grain yield by an average of 8.9%, and enhanced lodging index (LI) (increasing lodging risk with a higher LI) at the 1st (+23%) and 3rd (+17%) internodes with no significant effect at the 2nd internode. Inorganic nitrogen (N) fertilization increased both rice yield (+42%) and LI at the 2nd (+31%) and 3rd (+23%) internodes, but did not significantly affect LI at the 1st internode. The application of silicon (Si) and potassium (K) fertilizers increased rice yield by 7.2% and 18%, respectively, while simultaneously reducing LI by 14% and 19% at the 1st internode, by 15% and 21% at the 2nd internode, and by 4.5% and 18% at the 3rd internode. Prohexadione calcium and uniconazole increased rice yield by 6.7% and 8.3%, respectively, while paclobutrazol had no significant effect on rice yield. Prohexadione calcium and uniconazole reduced LI by 14% and 21% at the 1st internode, by 26% and 31% at the 2nd internode, and by 16% and 54% at the 3rd internode, respectively, whereas paclobutrazol only reduced LI at the 3rd internode by 12%. In conclusion, the application of Si, K, prohexadione calcium, and uniconazole is a promising strategy for improving rice yield and reducing lodging risk. In addition, we suggest that high-yielding practices (e.g., hybrid rice and inorganic N fertilization) and lodging-resistant practices (e.g., the application of Si, K, and PGRs) should be combined to increase grain yield and simultaneously reduce lodging risk in rice paddies. [Display omitted] • Hybrid rice increased yield but boosted lodging risk. • Inorganic nitrogen fertilization raised yield while enhancing lodging risk. • Silicon and potassium fertilization promoted yield and lowered lodging risk. • Prohexadione calcium and uniconazole increased yield and reduced lodging risk. [ABSTRACT FROM AUTHOR]

Hearing loss (HL) is a prevalent sensorineural disorder, and is among the most etiologically heterogeneous disorders. With the advent of next-generation sequencing (NGS) technologies, hundreds of candidate genes can be analyzed simultaneously in a cost-effective manner. Ninety-four patients from 87 families diagnosed with non-syndromic or syndromic HL were enrolled. A custom-designed HL panel and clinical exome sequencing (CES) were applied to explore molecular etiology in the cohort, and the efficacy of the two panels was examined. The etiologic diagnosis for HL has been identified for 36 out of 87 probands (41.4%), 28 with an autosomal recessive (AR) inheritance pattern and 8 with an autosomal dominant (AD) pattern. Candidate variants in 18 different genes were identified in the study cohort, 10 with AR inheritance pattern and 8 with AD pattern. Fourteen of the variants identified in the study were novel. The custom-designed HL panel covers almost all known HL-associated genes, and can be used as an effective clinical diagnostic platform; CES evaluates all exons related to clinical symptoms, and is also suitable for clinical diagnosis of HL. Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with HL in the clinical practice. [ABSTRACT FROM AUTHOR]

• Kapok fiber with thin cell wall and large lumen was used as supporting material for PCM. • The composite made by kapok and hollow PET fibers encapsulated PCM by vacuum impregnation. • This composite demonstrated obvious thermal regulating capacity in the cooling/hot environment. • The composite demonstrated robust leakage resistance to laundry, pressure and heat/cooling cycling. • This composite has great potential for dynamic heat insulation and thermal regulation. Kapok fiber, an agricultural product, is a typical cellulosic fiber with the features of thin cell wall and large lumen. Herein, a microtubule-based composite with high porosity of 98.03 % was prepared using kapok fibers and hollow PET. The kapok fiber-based composite successfully encapsulated a phase change material (PCM), that is a fatty acid ester of myristic acid and tetradecyl alcohol (MA-TD), in the microtubules by vacuum impregnation. The SEM showed that the PCM was encapsulated in the lumens of the fibers with a calculated percentage of 40.5 %. This condition provided the composite a basic thermal insulation from air pockets in the composite and a dynamic thermal insulation from the PCM. The kapok/PET/MA-TD could absorb 76.8 J/g latent heat in the comfort temperature range of 24 °C – 42.3 °C or release 77.4 J/g latent heat in the comfort temperature range of 29.7 °C – 10.5 °C. It withstood repeated laundry and exhibited robust leakage resistance to continuous heating/cooling under pressure. In addition, the composite was successfully used to dynamically regulate the temperature with obvious thermal regulating capacity in the simulated cooling/hot environments. Such material will be a robust candidate for dynamic heat regulating and thermal insulating applications. [ABSTRACT FROM AUTHOR]