ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes.

Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. We describe seven previously unreported subjects including three novel variants in ALG13 and report a milder neurodevelopmental course. We also summarize the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals. We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear.

Comparing the bone mineral density among male patients with latent autoimmune diabetes and classical type 1 and type 2 diabetes, and exploring risk factors for osteoporosis.

AIMS: This study aimed to compare the bone mineral densities (BMDs) among male patients with latent autoimmune diabetes in adults (LADA), classical type 1 diabetes (T1DM), and type 2 diabetes (T2DM), and to examine the risk factors for developing low BMD in these patients. PATIENTS AND METHODS: Between January 2017 and October 2020, a total of 57, 67, and 223 male patients with LADA, classical T1DM, and T2DM, respectively, were recruited from the endocrinology department of Shanghai Tenth People's Hospital. Hormonal markers of bone metabolism, lipid profiles, uric acid, glycosylated hemoglobin A1c (HbA1c), and beta-cell function were measured using blood samples. BMD was measured at the lumbar spine, femoral neck, and right hip by dual-energy X-ray absorptiometry. RESULTS: The mean BMD values from all three skeletal sites in male patients with LADA were comparable to those with classical T1DM but were much lower than those with T2DM. After adjusting for confounding factors, multiple linear regression analysis demonstrated that in all male patients with diabetes, body mass index (BMI), uric acid, and fasting C-peptide showed significant positive associations with BMD at all three skeletal sites; however, osteocalcin showed a negative association at all three sites. CONCLUSIONS: Compared with male patients with T2DM, lower BMDs were observed in patients with LADA and T1DM. Low BMI, uric acid, C-peptide levels, and high osteocalcin levels are risk factors for developing low BMD in male patients with diabetes.

[Application of multi-stage competing risk model to survival data].

The traditional proportional hazard model is commonly used to investigate the association between main outcome and predictor variables. However, the endpoints in medical studies are often not unique. The analyses of labeling other competing outcomes other than the main outcome as censored data will theoretically lead to a biased estimate of the risk of main outcome. Although the traditional competitive risk model can adjust the influence of other outcomes on the risk of the main outcome, it can not directly compare the differences on the risks of different outcomes. The multi-state competing risk model provides a relatively suitable solution for this problem. In this study, based on a previously published follow-up data set for prostate cancer patients, we developed traditional proportional hazard model, traditional competitive risk model, and multi-state competing risk model, respectively. By comparing the advantages and disadvantages of the three models with the same survival data, we clarified the clinical application value of the multi-state competitive risk model in survival data with multiple outcomes.

[Potential pleiotropism of cancer-related single nucleotide polymorphisms among Chinese population].

Objective: To investigate the potential pleiotropism of cancer-related single nucleotide polymorphisms (SNPs) among Chinese population. Methods: Based on the catalogue of GWAS jointly constructed by the National Human Genome Research Institute and the European Institute of Bioinformatics, according to population origin (Chinese population and non-Chinese population) and disease traits (cancer and non-cancer traits). All SNPs found by GWAS before August 2020 were divided into four categories: cancer in Chinese population, non-cancer in Chinese population, cancer in non-Chinese population and non-cancer in non-Chinese population. The number, correlation and linkage of the four categories of SNPs were described. Results: By August 2020, a total of 196 813 SNPs from 4 096 GWAS were included in the GWAS directory. The information that SNPs refer to unknown or were not related to the disease was excluded, and 117 441 independent SNPs were finally included. There were 619 SNPs related to cancer and 9 569 SNPs related to non-cancer disease in Chinese population, respectively. There were 4 624 SNPs related to cancer and 106 448 SNPs related to non-cancer disease (trait) in non-Chinese population, respectively. Three SNPs, rs2736100, rs6983267 and rs401681, were associated with two or more types of cancer in both Chinese and non-Chinese populations. Seven SNPs, rs7705526, rs2736100, rs10993994, rs2735839, rs4430796, rs174537 and rs9271588, were associated with cancer and non-cancer diseases in both Chinese and non-Chinese populations, respectively. Conclusion: There is a potential pleiotropism of cancer-related SNPs in Chinese population.

Ultrafast Transient Spectroscopy of Trans-Polyacetylene in the Midinfrared Spectral Range.

Trans-polyacetylene [t-(CH)_{x}] possesses twofold ground state degeneracy. Using the Su-Schrieffer-Heeger Hamiltonian, scientists predicted charged solitons to be the primary photoexcitations in t-(CH)_{x}; this prediction, however, has led to sharp debate. To resolve this saga, we use subpicosecond transient photomodulation spectroscopy in the mid-IR spectral range (0.1-1.5 eV) in neat t-(CH)_{x} thin films. We show that odd-parity singlet excitons are the primary photoexcitations in t-(CH)_{x}, similar to many other nondegenerate π-conjugated polymers. The exciton transitions are characterized by two photoinduced absorption (PA) bands at 0.38 and 0.6 eV, and an associated photoluminescence band at ∼1.5 eV having similar polarization memory. The primary excitons undergo internal conversion within ∼100 fs to an even-parity (dark) singlet exciton with a PA band at ∼1.4 eV. We also find ultrafast photogeneration of charge polarons when pumping deep into the polymer continuum band, which are characterized by two other PA bands in the mid-IR and associated photoinduced IR vibrational modes.

Surprisingly good thermoelectric performance of a black phosphorus/blue phosphorus van der Waals heterostructure.

Thermoelectric properties of a black phosphorus/blue phosphorus van der Waals heterostructure are investigated by using first-principles calculations and Boltzmann transport theory for both electrons and phonons. It is found that the heterostructure is both energetically and kinetically stable even at higher temperature. Compared with those of the constituent black and blue phosphorus monolayers, the thermoelectric performance of the heterostructure is significantly enhanced due to sharply decreased thermal conductivity caused by the presence of van der Waals interactions, as well as obviously reduced band gaps and multi-valley structures resulting from type-II band alignment. As a consequence, the room temperature ZT value can reach 1.6, which is much higher than those of the components. Furthermore, we obtain ZT over 2.0 in a wide temperature range from 400 to 800 K, and a maximum ZT of ∼3.2 can be realized at 700 K, which is surprisingly good for systems consisting of light elements only.

Structural and Functional Enrichment Analyses for Antimicrobial Peptides.

Whether there is any inclination between structures and functions of antimicrobial peptides (AMPs) is a mystery yet to be unraveled. AMPs have various structures associated with many different antimicrobial functions, including antibacterial, anticancer, antifungal, antiparasitic and antiviral activities. However, none has yet reported any antimicrobial functional tendency within a specific category of protein/peptide structures nor any structural tendency of a specific antimicrobial function with respect to AMPs. Here, we examine the relationships between structures categorized by three structural classification methods (CATH, SCOP, and TM) and seven antimicrobial functions with respect to AMPs using an enrichment analysis. The results show that antifungal activities of AMPs were tightly related to the two-layer sandwich structure of CATH, the knottin fold of SCOP, and the first structural cluster of TM. The associations with knottin and TM Cluster 1 even sustained through the AMPs with a low sequence identity. Moreover, another significant mutual enrichment was observed between the third cluster of TM and anti-Gram-positive-bacterial/anti-Gram-negative-bacterial activities. The findings of the structure-function inclination further our understanding of AMPs and could help us design or discover new therapeutic potential AMPs.

Functional integrity of honeybee (Apis mellifera L.) resistant to dieldrin γ-aminobutyric acid receptor channels conjugated with three fluorescent proteins.

To generate an efficient tool used in Xenopus oocyte expression for in situ investigation of channel receptor expression, distribution and function, the C-terminus of the honeybee (Apis mellifera L.) resistant to dieldrin (RDL) subunit was fused with *FP, including monomeric red, enhanced yellow or enhanced green fluorescent protein (referred to as mRFP, EYFP and EGFP, respectively). In the present study, all fused *FP-AmRDLs could be visualized using fluorescence and laser confocal microscopy in cRNA-injected oocytes. Fluorescence was distributed isotropically in the cellular membrane. The potencies of the agonist γ-aminobutyric acid (GABA), but not ß-alanine, and the test antagonists (fipronil, flufiprole, dieldrin, α-endosulfan, bifenazate and avermectin B1a) in the *FP-AmRDL receptor did not significantly differ from that of the untagged receptor with two-electrode voltage clamp detection. The half maximal effective concentrations (EC50 s) of GABA in AmRDL, EGFP-AmRDL, EYFP-AmRDL and mRFP-AmRDL receptors were 11.98, 12.61, 18.92 and 22.11 µM, respectively, and those of ß-alanine were 651.6, 629.6, 1643.0 and 2146.0 µM, respectively. Inhibition percentages of test antagonists against *FP-AmRDL and AmRDL were not significantly different from each other. Overall, the consistency in functional properties between *FP-AmRDL and AmRDL receptors makes pGH19-*FP a promising tool for further in situ investigation of GABA receptors.

Immunoregulation effects of TIM-3 on tumors.

Cancer poses a serious threat to human health and its increasing incidence has made it one of the most common causes of death. Immune factors affect in vivo tumor cell survival and expansion, and cancer patients have obvious cell immune dysfunction and low anti-tumor immunity. TIM-3 can be widely expressed in a variety of immune cells and it affects both innate and adaptive immune response by regulating the function of immune cells, thus affecting tumor occurrence and development. This paper focuses on the TIM-3 regulation of immune cells, and its expression and mechanism in patients with liver, gastric and prostate cancers in order to explore its regulatory mechanism in tumor immunity and provide new ideas and targets for tumor immunotherapy.

Ryanodine receptor genes of the rice stem borer, Chilo suppressalis: Molecular cloning, alternative splicing and expression profiling.

The ryanodine receptor (RyR) of the calcium release channel is the main target of anthranilic and phthalic diamide insecticides which have high selective insecticidal activity relative to mammalian toxicity. In this study, the full-length cDNA of Chilo suppressalis RyR (CsRyR) was isolated and characterized. The CsRyR mRNA has an open reading frame (ORF) of 15,387bp nucleotides, which encodes 5128 amino acids with GenBank ID: KR088972. Comparison of protein sequences showed that CsRyR shared high identities with other insects of 77-96% and lower identity to mammals and nematodes with only 42-45%. One alternative splicing site (KENLG) unique to Lepidoptera was found and two exclusive exons of CsRyR (I /II) were revealed. Spatial and temporal expression of CsRyR mRNA was at the highest relative level in 3rd instar larvae and head (including brain and muscle), and at the lowest expression level in egg and fat body. The expression levels of whole body CsRyR mRNA were increased remarkably after injection of 4th instar larvae with chlorantraniliprole at 0.004 to 0.4µg/g. This structural and functional information on CsRyR provides the basis for further understanding the selective action of chlorantraniliprole and possibly other diamide insecticides.

Reduced breast milk feeding subsequent to cosmetic breast augmentation surgery.

OBJECTIVE: To determine the effect of cosmetic breast augmentation on subsequent infant feeding. PARTICIPANTS, DESIGN AND SETTING: Population-based record linkage study of women giving birth in New South Wales, January 2006 - December 2011. Birth records were linked longitudinally to maternal hospitalisations up to 11 years before birth. Breast augmentation was identified by surgical procedure codes in hospital records. MAIN OUTCOME MEASURES: Any breast milk feeding at discharge from birth care, and among infants receiving any breast milk, exclusive breast milk feeding. The before-and-after effect of breast augmentation was assessed among women who had the surgery between births. RESULTS: Among 378 389 women who gave birth in the study period, 892 (0.2%) had prior breast augmentation. Among women with breast augmentation, 705 (79%) provided any breast milk to their infant at discharge, compared with 89% among women without augmentation. After adjusting for sociodemographic and pregnancy factors, infants of women with breast augmentation were less likely to receive breast milk at discharge than infants of women without augmentation (adjusted relative risk [ARR], 0.90; 95% CI, 0.87-0.93). However, infants receiving breast milk were not more or less likely to receive breast milk exclusively (ARR, 0.99; 95% CI, 0.97-1.01). Women with augmentation surgery between births changed their breastfeeding behaviour (reduced rates), while those with no augmentation or augmentation before both births did not. CONCLUSIONS: Reduced rates of breast milk feeding among women who have undergone breast augmentation underscore the importance of identifying, supporting and encouraging women who are vulnerable to a lower likelihood of breastfeeding.

Cryoprotective Effect and Optimal Concentration of Trehalose on Aortic Valve Homografts.

BACKGROUND AND AIM OF THE STUDY: Cryopreservation allows for the long-term storage of aortic homografts, but a high risk of calcification and degeneration is often observed following their transplantation. The study aim was to investigate the cryoprotective effect of trehalose on aortic valve homografts preserved in liquid nitrogen, and to determine the optimal trehalose concentration for such purpose. METHODS: Aortic valve homografts obtained from New Zealand White rabbits were processed using different protectants. Samples were assigned at random to four groups: a control group treated with dimethyl sulfoxide (DMSO; 0.1 mol/l), and test groups A, B and C, which were treated with 0.1 mol/l trehalose + 0.1 mol/l DMSO, 0.2 mol/l trehalose + 0.1 mol/l DMSO, or 0.3 mol/l trehalose + 0.1 mol/l DMSO, respectively, as protectant. Samples in each group were allocated randomly to three subgroups and cryopreserved for 12, 15, and 18 months, respectively. After thawing, apoptosis of the cryopreserved homograft samples was evaluated using immunohistochemistry, semi-quantitative RT-PCR and Western blotting methods. The viability of the tissue cells was assessed by monitoring glucose utilization capacity. RESULTS: The apoptosis assay showed that, among the four groups and at all time points, the expression of caspase-3 was lowest in test groups A and B and highest in the DMSO group. In comparison, the glucose metabolic rates of test groups A and B were highest, while rates for test group C and the control (DMSO) group ranked second and third. CONCLUSION: When aortic homografts are preserved in liquid nitrogen, the cryoprotective effect of trehalose combined with DMSO was superior to that of DMSO alone. The optimal trehalose concentration to cryoprotect rabbit aortic homografts was between 0.1 and 0.2 mol/l.

Overwhelming postsplenectomy infection.

This report aims to deepen the understanding of the pathogenesis, diagnosis, clinical characteristics, and treatment of overwhelming postsplenectomy infection (OPSI). A patient treated at Taihe Hospital for tuberculous OPSI is described, and relevant literature is reviewed. Broad-spectrum antibiotics, suppression of the systemic inflammatory reaction, and anti-shock measures were the keys to the successful treatment of this condition. OPSI is a life-threatening condition and has a high mortality rate. Early diagnosis, use of anti-inflammatory glucocorticoids, and administration of high-dose gamma globulin and ulinastatin for the treatment of OPSI may improve outcomes.

Post-surgical treatment of a patient with ectopic pheochromocytoma.

We report here the course and treatment of a patient with ectopic pheochromocytoma. The patient was cured after treatment with respiratory and circulatory support, multiple-organ protection, and continuous renal replacement therapy (CRRT) for approximately 2 weeks. After misdiagnosis, a patient with ectopic pheochromocytoma who is being treated should undergo aggressive fluid supplementation and CRRT instead of central venous pressure measurement, which has limited value in guiding fluid supplementation. The main priority is maintaining hypotension. Hypertension may be controlled with rapid-acting agents. A good outcome can be anticipated for patients who undergo comprehensive intensive care unit therapy.

Influence of Rho kinase inhibitor fasudil on late endothelial progenitor cells in peripheral blood of COPD patients with pulmonary artery hypertension.

OBJECTIVE: To investigate the influence of Fasudil, a Rho inhibitor on the number and functions of the late endothelial progenitor cells in peripheral blood of chronic obstructive pulmonary diseases (COPD) patients with pulmonary artery hypertension. BACKGROUND: It is not clear yet, whether Rho Kinase Inhibitor Fasudil can reduced pulmonary artery pressure through improving lung endothelial function. METHODS: 80 COPD patients with pulmonary artery hypertension were selected and divided into two groups: the treatment group and the control group, which had 40 patients, respectively. Changes in the number and function of the late endothelial progenitor cells in peripheral blood of the patients before and after the treatment were compared between the two groups. The changes on the pulmonary artery pressure were also compared. RESULTS: The number of the late endothelial progenitor cells in peripheral blood of the treatment group increased and the function was enhanced. The pulmonary artery pressure was reduced. The difference before and after the treatment and with the control group was statistically significant (p < 0.05). CONCLUSIONS: The Rho-kinase inhibitor Fasudil increased the number and enhanced the function of the late endothelial progenitor cells in peripheral blood of COPD patients with pulmonary artery hypertension (Tab. 3, Fig. 2, Ref. 17).

Refractive index sensor based on the leaky radiation of a microfiber.

In this work we present a refractive index sensor based on the leaky radiation of a microfiber. The 5.3um diameter microfiber is fabricated by drawing a commercial optical fiber. When the microfiber is immersed into a liquid with larger refractive index than the effective index of fiber mode, the light will leak out through the leaky radiation process. The variation of refractive index of liquid can be monitored by measuring radiation angle of light. The refractive index sensitivity can be over 400 degree/RIU in theory. In the experiment, the variation value 0.001 of refractive index of liquid around this microfiber can be detected through this technique. This work provides a simple and sensitive method for refractive index sensing application.

Periodontitis and the risk of oral, gastric and esophageal cancers: a two-sample Mendelian randomization study.

BACKGROUND: Periodontitis is a common oral disease and the chronic inflammation caused by it may influence the development of cancers in the upper gastrointestinal tract. Many observational studies have established a relationship between the two, but the results are not entirely consistent. METHODS: Two-sample MR was performed using publicly available genome-wide association studies data for periodontitis, oral, gastric and oesophagal cancers. The Inverse Variance Weighting (IVW) method serves as the primary method, with MR Egger, Weighted Median, Simple Model and Weighted Model Algorithm methods as complementary methods to assess genetic causal associations. Cochran Q-test, MR-Egger regression and MR polytropic residuals and outliers were used to assess heterogeneity and horizontal pleiotropy. RESULTS: IVW results did not support a causal association between periodontitis and oral (OR = 1.00, 95% CI: 1.00, 1.00) and oesophagal cancer (OR = 1.00, 95% CI: 1.00, 1.00). Similarly, there was again no causal association between periodontitis and gastric cancer, which was integrated with an OR of 1.04 (95% CI: 0.97, 1.12). Complementary method results were consistent with IVW and heterogeneity and horizontal pleiotropy were not found in most studies. CONCLUSIONS: The findings of our MR study do not support a causal relationship between periodontitis and oral, gastric and oesophagal cancers.

X-linked markers in the Duchenne muscular dystrophy gene associated with oral clefts.

As part of an international consortium, case-parent trios were collected for a genome-wide association study of isolated, non-syndromic oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP). Non-syndromic oral clefts have a complex and heterogeneous etiology. Risk is influenced by genes and environmental factors, and differs markedly by gender. Family-based association tests (FBAT) were used on 14,486 single nucleotide polymorphisms (SNPs) spanning the X chromosome, stratified by type of cleft and racial group. Significant results, even after multiple-comparisons correction, were obtained for the Duchenne muscular dystrophy (DMD) gene, the largest single gene in the human genome, among CL/P (i.e., both CL and CLP combined) trios. When stratified into groups of European and Asian ancestry, stronger signals were obtained for Asian subjects. Although conventional sliding-window haplotype analysis showed no increase in significance, selected combinations of the 25 most significant SNPs in the DMD gene identified four SNPs together that attained genome-wide significance among Asian CL/P trios, raising the possibility of interaction between distant SNPs within the DMD gene.

Transformation bending device emulated by graded-index waveguide.

We demonstrate that a transformation device can be emulated using a gradient-index waveguide. The effective index of the waveguide is spatially varied by tailoring a gradient thickness dielectric waveguide. Based on this technology, we demonstrate a transformation device guiding visible light around a sharp corner, with low scattering loss and reflection loss. The experimental results are in good agreement with the numerical results.

Simple way for achieving passive all-optical switching of continuous waves lasers using pure nematic liquid crystal.

We have examined pure nematic liquid crystal (LC), 4'-pentyl-4-biphenylcarbonitrile (5-CB), with a 90° twisted alignment within a cell made of two cross-polarized absorptive plastic polarizers, and investigated the nonlinear transmission properties using cw (532 nm) lasers. We observed optically self-activated polarization switching with a factor of three lower switching power than a dye-doped LC cell with similar linear transmittance using glass substrates. We also studied the dynamics of the switching processes and observed millisecond switching time. These studies have demonstrated a simpler but more efficient way for fabricating broadband, low switching power, millisecond time scale switching, and optical limiting devices.