Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation.

Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane. In this study, we find that Hsc70 promotes PD-L1 degradation through the endosome-lysosome pathway and reduces PD-L1 recycling to the cell membrane. This effect is dependent on Hsc70-PD-L1 binding which inhibits the CMTM6-PD-L1 interaction. We further identify an Hsp90α/ß inhibitor, AUY-922, which induces Hsc70 expression and PD-L1 lysosomal degradation. Either Hsc70 overexpression or AUY-922 treatment can reduce PD-L1 expression, inhibit tumor growth and promote anti-tumor immunity in female mice; AUY-922 can further enhance the anti-tumor efficacy of anti-PD-L1 and anti-CTLA4 treatment. Our study elucidates a molecular mechanism of Hsc70-mediated PD-L1 lysosomal degradation and provides a target and therapeutic strategies for tumor immunotherapy.

A novel hemizygous CD40L mutation of X-linked hyper IgM syndromes and compound heterozygous DOCK8 mutations of hyper IgE syndromes in two Chinese families.

X-linked hyper-immunoglobulin M (X-HIGM) syndrome and autosomal recessive hyper-immunoglobulin E syndrome (HIES) are rare inborn errors of immunity characterized by recurrent infections due to immune system impairment. In this study, we identified a novel hemizygous CD40 ligand (CD40L) mutation and compound heterozygous dedicator of cytokinesis-8 (DOCK8) mutations in two Han Chinese families with X-HIGM and HIES, respectively. We aimed to investigate the association between their genotypes and phenotypes. Genomic DNA was extracted from peripheral blood samples obtained from the families. Whole exome sequencing and Sanger sequencing were performed to identify and verify pathogenic variants in the two families. Clinical analyses of the probands were also performed. A novel hemizygous mutation of CD40L in exon 2 (c.257delA) was identified in the first proband, resulting in the substitution of glycine with glutamic acid at codon 86 of the protein. This leads to premature termination of translation at downstream codon 9 (p.E86Gfs*9). Sanger sequencing confirmed that the variant was inherited from the mother. The second proband carried two novel compound heterozygous mutations in DOCK8: one at exon 14 (c.1546C > G) inherited from the father, and the other at intron 41 (c.5355 + 6C > T; splicing) inherited from the mother. This study enhances our understanding of the pathogenetic mutation spectrum of CD40L and DOCK8 genes, facilitating the prenatal diagnosis of X-HIGM and HIES and enabling timely treatment of patients.

JAG1 Variants Confer Genetic Susceptibility to Thyroid Dysgenesis and Thyroid Dyshormonogenesis in 813 Congenital Hypothyroidism in China.

Background and Objective: Congenital hypothyroidism (CH) is indeed a prevalent neonatal endocrine disorder, affecting approximately 1 in 2000-3000 newborns worldwide, and 1 in 2400 newborns in China. Despite its high incidence, the genetic causes of CH, particularly those related to thyroid dysgenesis (TD), are still not well understood. However, previous studies have suggested that JAG1 may be a potential susceptibility gene for congenital thyroid defects. To explore the association between JAG1 and CH, we screened JAG1 variants in a large cohort of 813 CH patients. Methods: We performed genetic analysis of JAG1 using next-generation sequencing in 813 CH cases. The pathogenicity of the variants was assessed by bioinformatics softwares, protein sequence conservation analysis, and hydrophobic analysis. Further genetic analysis was conducted targeting 20 CH-related genes in these 25 JAG1 variant carriers. Results: We identified 10 pathogenic missense mutations (p.V45L, p.V272I, p.P552L, p.G610E, p.G852D, p.A891T, p.E1030K, p.R1060W, p.A1131T, p.P1174L) carried by 25 patients, the mutation rate of JAG1 in CH was 3.08%. Among these 25 patients, 16 with 1 variant, 6 with 2 variants, and the other 3 with 3 variants. Our findings indicated that JAG1 variants confer genetic susceptibility to both TD and DH, but with different inheritance models. JAG1 variants lead to TD mainly through monogenic model, while for DH cases, both monogenic mechanisms and oligogenic mechanisms play a pivotal role. Oligogenicity may contribute to the disease severity of DH. Conclusion: JAG1 is a shared genetic factor in TD and DH, with a detection rate of 3.08% in Chinese individuals with CH. A comparison between the oligogenic and monogenic groups suggests a gene dosage effect in CH. Patients with the same JAG1 mutation exhibit diverse clinical phenotypes, indicating complex mechanisms underlying phenotypic heterogeneity.

High-Performance Single-Crystal Lithium-Rich Layered Oxides Cathode Materials via Na2WO4-Assisted Sintering.

Single-crystal lithium-rich layered oxides (LLOs) with excellent mechanical properties can enhance their crystal structure stability. However, the conventional methods for preparing single-crystal LLOs, require large amounts of molten salt additives, involve complicated washing steps, and increase the difficulty of large-scale production. In this study, a sodium tungstate (Na2WO4)-assisted sintering method is proposed to fabricate high-performance single-crystal LLOs cathode materials without large amounts of additives and additional washing steps. During the sintering process, Na2WO4 promotes particle growth and forms a protective coating on the surface of LLOs particles, effectively suppressing the side reactions at the cathode/electrolyte interface. Additionally, trace amounts of Na and W atoms are doped into the LLOs lattice via gradient doping. Experimental results and theoretical calculations indicate that Na and W doping stabilizes the crystal structure and enhances the Li+ ions diffusion rate. The prepared single-crystal LLOs exhibit outstanding capacity retention of 82.7% (compared to 65.0%, after 200 cycles at 1 C) and a low voltage decay rate of 0.76 mV per cycle (compared to 1.80 mV per cycle). This strategy provides a novel pathway for designing the next-generation high-performance cathode materials for Lithium-ion batteries (LIBs).

Mechanism of Cold Plasma Combined with Glycation in Altering IgE-Binding Capacity and Digestion Stability of Tropomyosin from Shrimp.

Tropomyosin (TM) is a major crustacean allergen, and the present studies have tried to reduce its allergenicity by processing technologies. However, most research stopped on the allergenicity and structure of allergens, while information about epitopes was less. In this study, we first investigated the effects of cold plasma (CP) combined with glycation (CP-G) treatment on the processing and trypsin cleavage sites of TM from shrimp (Penaeus chinensis). The results showed a significant reduction in the IgE-binding capacity of TM after CP-G treatment, with a maximum reduction of 30%. This reduction was associated with the combined effects: modification induced by CP destroyed the core helical structure (D137 and E218) and occupied the potential glycation sites, leading to sequent glycation on conserved areas of TM, especially the epitope L130-Q147. Additionally, CP-G treatment decreased the digestion stability of TM by increasing the number of cleavage sites of trypsin and improving the efficiency of some sites, including K5, K6, K30, and R133, resulting in a lower IgE-binding capacity of digestion products, which fell to a maximum of 20%. Thus, CP-G is a valuable and reliable processing technology for the desensitization of aquatic products.

ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade.

Despite advances in cancer treatment, immune checkpoint blockade (ICB) only achieves complete response in some patients, illustrating the need to identify resistance mechanisms. Using an ICB-insensitive tumor model, here we discover cisplatin enhances the anti-tumor effect of PD-L1 blockade and upregulates the expression of Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) in tumors. Arih1 overexpression promotes cytotoxic T cell infiltration, inhibits tumor growth, and potentiates PD-L1 blockade. ARIH1 mediates ubiquitination and degradation of DNA-PKcs to trigger activation of the STING pathway, which is blocked by the phospho-mimetic mutant T68E/S213D of cGAS protein. Using a high-throughput drug screen, we further identify that ACY738, less cytotoxic than cisplatin, effectively upregulates ARIH1 and activates STING signaling, sensitizing tumors to PD-L1 blockade. Our findings delineate a mechanism that tumors mediate ICB resistance through the loss of ARIH1 and ARIH1-DNA-PKcs-STING signaling and indicate that activating ARIH1 is an effective strategy to improve the efficacy of cancer immunotherapy.

What is the appropriate gravel size during ureteroscopy lithotripsy? An in vitro evaluation.

To propose the suitable diameter of calculus debris produced during flexible ureteroscopy lithotripsy (fURL). A glass tube was used to simulate the stone excretion process during Furl. Different stone diameters (0.50-1.00 mm, 0.25-0.50 mm, and 0.10-0.25 mm) with three sizes of flexible ureteroscopy (fURS) (7.5Fr, 8.7Fr, and 9.9Fr) and ureteral access sheath (UAS) (12/14Fr) with or without negative pressure suction were employed in the experiment. The intraoperative calculi excretion (ICE) was recorded according to the stones discharged from the gap between fURS and UAS. The ICE raised significantly in thinner fURS and UAS due to the smaller Ratio of Endoscope-Sheath Diameter (RESD). The gravel size ≤ 0.25 mm was conducive to drainage with traditional UAS, while using fURS with negative-pressure UAS could significantly improve ICE. The gravel size ≤ 0.5 mm was conducive to expulsion. We clarify that ICE during ureteroscopy relates to RESD and negative pressure suction. The proper size of the stone fragment is critical in ensuring the expulsion during fURL, ≤ 0.25 mm in traditional UAS and ≤ 0.50 mm in negative-pressure UAS, respectively.

Changing the IgE Binding Capacity of Tropomyosin in Shrimp through Structural Modification Induced by Cold Plasma and Glycation Treatment.

Tropomyosin (TM) is the major allergen of shrimp (Penaeus chinensis). Previous studies showed that separate cold plasma or glycation have their drawback in reducing allergenicity of TM, including effectiveness and reliability. In the current study, a new processing combining cold plasma (CP) and glycation was proposed and its effect on changing IgE binding capacity of TM from shrimp was investigated. Obtained results showed the IgE binding capacity of TM was reduced by up to 40% after CP (dielectric barrier discharge, 60 kV, 1.0 A) combined with glycation treatment (4 h, 80 °C), compared with the less than 5% reduction after single CP or glycation treatment. Notably, in contrast to the general way of CP prompting glycation, this study devised a new mode of glycation with ribose after CP pretreatment. The structural changes of TM were explored to explain the decreased IgE binding reactivity. The results of multi-spectroscopies showed that the secondary and tertiary structures of TM were further destroyed after combined treatment, including the transformation of 50% α-helix to ß-sheet and random coils, the modification and exposure of aromatic amino acids, and the increase of surface hydrophobicity. The morphology analysis using atomic force microscope revealed that the combined processing made the distribution of TM particles tend to disperse circularly, while it would aggregate after either processing treatment alone. These findings confirmed the unfolding and reaggregation of TM during combined processing treatment, which may result in the remarkable reduction of IgE binding ability. Therefore, the processing of CP pretreatment combined with glycation has the potential to reduce or even eliminate the allergenicity of seafood.

Comprehensive Analysis of the Structure and Allergenicity Changes of Seafood Allergens Induced by Non-Thermal Processing: A Review.

Seafood allergy, mainly induced by fish, shrimp, crab, and shellfish, is a food safety problem worldwide. The non-thermal processing technology provides a new method in reducing seafood allergenicity. Based on the structural and antigenic properties of allergenic proteins, this review introduces current methods for a comprehensive analysis of the allergenicity changes of seafood allergens induced by non-thermal processing. The IgE-binding capacities/immunoreactivity of seafood allergens are reduced by the loss of conformation during non-thermal processing. Concretely, the destruction of native structure includes degradation, aggregation, uncoiling, unfolding, folding, and exposure, leading to masking of the epitopes. Moreover, most studies rely on IgE-mediated assays to evaluate the allergenic potential of seafood protein. This is not convincing enough to assess the effect of novel food processing techniques. Thus, further studies must be conducted with functional assays, in vivo assays, animal trials, simulated digestion, and intestinal microflora to strengthen the evidence. It also enables us to better identify the effects of non-thermal processing treatment, which would help further analyze its mechanism.

Acute pulmonary embolism and severe post thrombolysis renal bleeding, two deadly complications following mini-percutaneous nephrolithotomy: a rare case report.

BACKGROUND: Acute pulmonary embolism and severe renal bleeding are two lethal postoperative complications, but there has been no report that involves both of them after mini-percutaneous nephrolithotomy. CASE PRESENTATION: A 62-year-old woman was admitted to our hospital with extremely severe hydronephrosis and multiple right renal calculi. After thorough examination, she received prone-position mini-percutaneous nephrolithotomy under spinal anaesthesia. Three days postoperatively, the patient complained of chest pain and dyspnea. Computed tomography pulmonary angiogram (CTPA) showed multiple embolisms in the left pulmonary artery and its branches. Symptoms were relieved after anticoagulant and thrombolysis therapy. On the 6th postoperative day, the patient developed shortness of breath, computed tomography angiography (CTA) showed massive hemorrhage in the right kidney, diffused contrast medium in the middle and lower part of the right kidney was seen during digital substraction angiography (DSA). Superselective right renal artery embolization (SRAE) was then applied using coil to occlude the responsible artery. The patient generally recovered under conscientious care and was approved to be discharged 26 days postoperatively. CONCLUSIONS: This is the first case that involved both acute pulmonary embolism and severe post thrombolysis renal bleeding. The importance of D-dimer in the prediction and early detection of pulmonary embolism should be noted. For post thrombolysis renal bleeding, SRAE is considered as a reliable treatment.

Extraordinary p-d Hybridization Interaction in Heterostructural Pd-PdSe Nanosheets Boosts C-C Bond Cleavage of Ethylene Glycol Electrooxidation.

Advanced electrocatalysts for complete oxidation of ethylene glycol (EG) in direct EG fuel cells are strongly desired owing to the higher energy efficiency. Herein, Pd-PdSe heterostructural nanosheets (Pd-PdSe HNSs) have been successfully fabricated via a one-step approach. These Pd-PdSe HNSs feature unique electronic and geometrical structures, in which unconventional p-d hybridization interactions and tensile strain effect co-exist. Compared with commercial Pd/C and Pd NSs catalysts, Pd-PdSe HNSs display 5.5 (6.6) and 2.5 (2.6) fold enhancement of specific (mass) activity for the EG oxidation reaction (EGOR). Especially, the optimum C1 pathway selectivity of Pd-PdSe HNSs reaches 44.3 %, illustrating the superior C-C bond cleavage ability. Electrochemical in situ FTIR spectroscopy and theoretical calculations demonstrate that the extraordinary p-d hybridization interaction and tensile strain effect could effectively reduce the activation energy of C-C bond breaking and accelerate CO* oxidation, boosting the complete oxidation of EG and improving the catalytic performance.

Nicotinamide nucleotide transhydrogenase mutation analysis in Chinese patients with thyroid dysgenesis.

Thyroid dysgenesis (TD) accounts for 80% cases of congenital hypothyroidism, which is the most common neonatal disorder. Until now, the gene mutations have been reported associated with TD can only account for 5% cases, suggesting the genetic heterogeneity of the pathology. Nicotinamide nucleotide transhydrogenase (NNT) plays a crucial role in regulating redox homeostasis, patients carrying NNT mutations have been described with a clinical phenotype of hypothyroidism. As TD risk is increased in the context of several syndromes and redox homeostasis is vital for thyroid development and function, NNT might be a candidate gene involved in syndromic TD. Therefore, we performed target sequencing (TS) in 289 TD patients for causative mutations in NNT and conducted functional analysis of the gene mutations. TS and Sanger sequence were used to screen the novel mutations. For functional analysis, we performed western blot, measurement of NADPH/NADPtotal and H2 O2 generation, cell proliferation, and wounding healing assay. As a result, three presumably pathogenic mutations (c.811G > A, p.Ala271Ser; c.2078G > A, p.Arg693His; and c.2581G > A, p.Val861Met) in NNT had been identified. Our results showed the damaging effect of NNT mutations on stability and catalytic activity of proteins and redox balance of cells. In conclusion, our findings provided novel insights into the role of the NNT isotype in thyroid physiopathology and broaden the spectrum of pathogenic genes associated with TD. However, the pathogenic mechanism of NNT in TD is still need to be investigated in further study.

[Re discussion on arthroscopic repair of rotator cuff tear in aged patients].

OBJECTIVE: To investigate the method and clinical effects of modified anchor insertion with single-row suture arthroscopic rotator cuff repair for aged patients with rotator cuff tear. METHODS: From March 2016 to February 2020, 96 aged patients with rotator cuff tears were retrospectively analyzed, including 29 males and 67 females, aged from 65 to 85 years, with a mean of (68.8±3.9) years. Patients were treated with modified anchor insertion with single-row suture arthroscopic rotator cuff repair technique. Before and after operation, University of California Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score were used to evaluate shoulder joint function, visual analogue scale (VAS)was used to evaluate patients' pain. Among them, 32 patients underwent magnetic resonance examination one year postoperatively. RESULTS: All operations were completed and the patients were followed up from 11 to 42 months, with a mean of (21.4±7.5) months. The UCLA score increased from preoperative 12.22±3.30 to final follow-up 31.30±2.49 (t=45.21, P<0.01);ASES score increased from preoperative 8.60±1.88 to final follow-up 12.60±0.84 (t=19.05, P<0.01);and the VAS decreased from preoperative 5.00 (2.00 to 8.00)scores to final follow-up 1.00 (0.00 to 3.00)scores (Z=-12.22, P<0.05). One year after operation, one of the 32 patients who underwent MRI showed that the repaired rotator cuff was torn again, but it did not affect the normal life and did not operate again. During the final follow-up, no anchor extraction was found in all 96 aged patients. CONCLUSION: Modified anchor insertion with single-row suture arthroscopic rotator cuff repair technique for rotator cuff tear in aged patients could achieve satisfactory results and effectively reduce the anchor extraction rate.

[Comparison of intramedullary nail fixation following two step closed reduction or limited open reduction for femoral subtrochanteric fractures].

OBJECTIVE: To compare clinical efficacy of intramedullary nail fixation following two-step closed reduction or limited open reduction for femoral subtrochanteric fractures. METHODS: Forty six patients with femoral subtrochanteric fractures were analyzed retrospectively from January 2014 to April 2020. Twenty four patients which including 16 males and 8 females, aged from 34 to 91 years old with an average of (55.42±18.25) years old, were treated with two step closed reduction and intramedullary nail fixation on supine position. Twenty-two patients which including 15 males and 7 females, aged from 33 to 87 years old with an average of (56.31±14.77) years old, were performed limited open reductionand intramedullary nail fixation. Operation time, intraoperative blood loss, complications and fracture healing time were recorded and compared between two groups. Postoperative Harris hip score at 8 months was applied to evalaute joint function. RESULTS: All patients were successfully complete operation without incision infection. All patients were followed up from 8 to 36 months with an average of (18.2± 6.1) months. Introperation blood loss, operation time in closed reduction group were (157.92±51.07) ml, (82.08±13.43) min respectively, while in limited open reduction group were (230.91±87.88) ml, (92.73±12.79) min respectively; while there were statistical difference between two groups (P<0.05). There was no difference in fracture healing time between two groups (P>0.05). There were 2 patients in each groups occurred pulmonary infection and healed after medical treatment. No statistical difference in postoperative Harris score at 8 months between closed reduction group (88.42±6.85) and limited open reduction group (88.55±6.31)(P>0.05). CONCLUSION: Femoral subtrochanteric fractures could be effectively treated by both methods. Two-step closed reduction and intramedullary nail fixation may be more advantageous in less tissue damage, shorter operation time and less intraoperative bleeding.

A Learning Sparrow Search Algorithm.

This paper solves the drawbacks of traditional intelligent optimization algorithms relying on 0 and has good results on CEC 2017 and benchmark functions, which effectively improve the problem of algorithms falling into local optimality. The sparrow search algorithm (SSA) has significant optimization performance, but still has the problem of large randomness and is easy to fall into the local optimum. For this reason, this paper proposes a learning sparrow search algorithm, which introduces the lens reverse learning strategy in the discoverer stage. The random reverse learning strategy increases the diversity of the population and makes the search method more flexible. In the follower stage, an improved sine and cosine guidance mechanism is introduced to make the search method of the discoverer more detailed. Finally, a differential-based local search is proposed. The strategy is used to update the optimal solution obtained each time to prevent the omission of high-quality solutions in the search process. LSSA is compared with CSSA, ISSA, SSA, BSO, GWO, and PSO in 12 benchmark functions to verify the feasibility of the algorithm. Furthermore, to further verify the effectiveness and practicability of the algorithm, LSSA is compared with MSSCS, CSsin, and FA-CL in CEC 2017 test function. The simulation results show that LSSA has good universality. Finally, the practicability of LSSA is verified by robot path planning, and LSSA has good stability and safety in path planning.

Construction of TiO2-MnO2 0D-2D nanostructured heterojunction for enhanced photocatalytic hydrogen production.

The low transfer efficiency and high recombination loss of photo-induced carriers in TiO2 are significant issues that hinder its photocatalytic activity. Herein, TiO2 nanoparticles (∼5 nm) were loaded on MnO2 nanosheets (40-60 nm) to form TiO2-MnO2 nanostructured heterojunction (0D-2D nanostructure unit), possessing a high specific surface area. The separation/transfer efficiency of photocarriers and the solar absorptivity of TiO2-MnO2 were improved, thus enhancing solar energy conversion efficiency. The enhanced transfer efficiency of carriers is associated with the 2D network of MnO2 and abundant oxygen vacancies serving as media for electron transport. The enhanced visible absorption and reduced recombination should be attributed to the narrowed bandgap and modified energy band structure. The photocurrent of TiO2-MnO2 increased obviously and the H2 production rate increased to 0.38 mmol g-1 h-1, compared with that of pure TiO2 (0.25 mmol g-1 h-1). The enhanced photocatalytic properties are also associated with the excellent water oxidation kinetics caused by MnO2 nanosheets.

Dual Oxidase System Genes Defects in Children With Congenital Hypothyroidism.

PURPOSE: The objectives of this study were to analyze the distribution of dual oxidase (DUOX) system genes (containing DUOX2, DUOX1, DUOXA2, and DUOXA1) variants in children with congenital hypothyroidism (CH) and their phenotypes. METHODS: Target region sequencing technology was performed on DUOX system genes among 606 CH subjects covering all the exon and intron regions. Detailed clinical data were collected for statistical analysis. RESULTS: A total of 95 suspected pathogenic variants were detected in the DUOX system genes, showing a 39.11% rate in variant carrying (237/606). DUOX2 had the highest rate in this study. There were statistical differences in maximum adjusted dose and current dose of levothyroxine between the DUOX system genes nonmutated group with the mutated group (both Ps < 0.001). The cases in the DUOX system genes mutated group were more likely to develop into transient CH (χ 2 = 23.155, P < 0.001) and more likely to manifested as goiter or gland-in-situ (χ 2 = 66.139, P < 0.001). In addition, there was no significant difference in clinical characteristics between DUOX system genes monoallelic and non-monoallelic. Although 20% of the variants affected the functional domain regions (EF hand, flavin adenine dinucleotide and nicotinamide adenine dinucleotide binding sites), there was no significant effect on the phenotype severity whether the variation is located in the functional domain regions. CONCLUSIONS: Our results showed the high variation rate of DUOX2 in the DUOX system genes among Chinese CH patients. The complex genotype-phenotype relationship of DUOX system genes broadened the understanding of CH phenotype spectrum.

Lingual nerve injury caused by laryngeal mask airway during percutaneous nephrolithotomy: A case report.

BACKGROUND: Lingual nerve injury (LNI) is a rare complication following the use of laryngeal mask airway (LMA). The occurrence of this unexpected complication causes uncomfortable symptoms in patients and worsens their quality of life. We present an unusual case of LNI caused by the use of an LMA in percutaneous nephrolithotomy (PCNL). CASE SUMMARY: A 49-year-old man presented to our hospital with a 3-year history of intermittent left lower back pain. Abdominal computed tomography showed a 25 mm × 20 mm stone in the left renal pelvis. PCNL surgery using LMA was performed to remove the renal stone. The patient reported numbness on the tip of his tongue after the operation, but there were no signs of swelling or trauma. The patient was diagnosed with LNI after other possible causes were ruled out. The symptom of numbness eventually improved after conservative medical therapy for 1 wk. The patient completely recovered 3 wk after surgery. CONCLUSION: This is the first case report describing LNI with the use of LMA in PCNL. In our case, an inappropriate LMA size, intraoperative movement, and a specific surgical position might be potential causes of this rare complication.

Fire extinguishing performance and mechanism for several typical dry water extinguishing agents.

In this work, four new dry water fire extinguishing agents (FEAs) were prepared by hydrophobic SiO2 and aqueous solution under certain conditions. The dry water FEAs were developed and we conducted two types of fire extinguishing experiments (i.e., class A solid fire and class B liquid fire test). Thermocouples and a color video camera were used to measure burning temperature and record the fire extinguishing process. Results indicate that the new dry water FEAs have the ability to extinguish A, B and C fires, and have a better cooling effect than dry powder FEA. It is noted, compared with traditional FEAs, that dry water FEAs have the advantages of high efficiency and high speed, and have a potential application prospect.

Identification and analyzes of DUOX2 mutations in two familial congenital hypothyroidism cases.

BACKGROUND: Mutations in DUOX2 are the frequent cause of congenital hypothyroidism (CH), a common neonatal metabolic disorder characterized by great phenotypic variability. CH can be traditionally subclassified into two subtypes: thyroid dysgenesis (TD) and thyroid dyshormonogenesis. The objectives of this study were to analyze the genetic data of two familial CH cases, to elucidate the pathogenesis from the perspective of genetics and to review and summarize the previous findings. METHODS: Targeted regions sequencing (TRS) technology covering all exons and intron-exon boundaries of 35 known and potential CH-related candidate target genes in combination with Sanger sequencing were performed to identify the likely pathogenic mutations of the six patients with familial CH. RESULTS: In family 1, two DUOX2 missense mutations, namely, c.1060C>T/p.R354W in exon 10 and c.3200C>T/p.S1067L in exon 25, were found. Patient 1 (P1), P2 and P3 were transient CH (TCH) patients with eutopic thyroid glands of normal size and function. In family 2, only the mutation c.3200C>T/p.S1067L was identified. P4, P5, and P6 were diagnosed with permanent CH (PCH), which requires lifelong levothyroxine (L-T4) treatment. Furthermore, both P4 and P5 harbored properly located thyroid glands, whereas P6 had a mildly reduced gland. P1, P3, P6, and other family members carrying monoallelic or biallelic DUOX2 mutations showed no obvious abnormal clinical symptoms or signs, while P2, P4, and P5 showed umbilical hernias. CONCLUSIONS: The present study suggests that the phenotypic features resulting from DUOX2 mutations vary greatly. The p.R354W and p.S1067L alterations or the combination of the two alterations in DUOX2 are probably only predisposing to CH and DUOX2 may be involved in the morphogenesis of the human thyroid gland. Simultaneously, the compensation of DUOX1 for the loss of DUOX2, undetectable pathogenic mutations, the effects of environmental factors, epigenetic mechanisms and the involvement of multiple genes cannot be excluded in the explanation of these genetic results.