Transcranial Temporal Interference Stimulation of the Right Globus Pallidus in Parkinson's Disease.

BACKGROUND: Invasive deep brain stimulation (DBS) has been shown to be effective in treating patients with Parkinson's disease (PD), yet its clinical use is limited to patients at the advanced stage of the disease. Transcranial temporal interference stimulation (tTIS) may be a novel nonneurosurgical and safer alternative, yet its therapeutic potential remains unexplored. OBJECTIVE: This pilot study aims to examine the feasibility and safety of tTIS targeting the right globus pallidus internus (GPi) for motor symptoms in patients with PD. METHODS: Twelve participants with mild PD completed this randomized, double-blind, and sham-controlled experiment. Each of them received either 20-minute or sham tTIS of the right GPi. Before and immediately after the stimulation, participants completed the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) in the "medication-on" state to assess the motor symptoms. The blinding efficacy and side effects were also assessed. RESULTS: tTIS was well tolerated by participants, with only mild, transient adverse effects reported. tTIS significantly reduced MDS-UPDRS-III scores by 6.64 points (14.7%), particularly in bradykinesia (23.5%) and tremor (15.3%). The left side showed more significant alleviation in motor symptoms, particularly bradykinesia, compared to the right side. Participants with severer bradykinesia and tremor before stimulation experienced greater improvement after tTIS. CONCLUSION: This pilot study suggests that the tTIS, as a novel noninvasive DBS approach, is feasible and safe for alleviating motor symptoms in mild PD, especially bradykinesia and tremor. Future larger-scale and more definitive studies are needed to confirm the benefits. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Study on the correlation between iris blood flow, iris thickness and pupil diameter in the resting state and after pharmacological mydriasis in patients with diabetes mellitus.

BACKGROUND: To investigate whether iris blood flow and iris thickness at the iris smooth muscle region affect the pupil diameter at rest and after drug-induced mydriasis in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: T1DM patients and healthy children were recruited from the SCADE cohort. T2DM patients and healthy adults were recruited from patients undergoing cataract surgery at Shanghai General Hospital. Iris vessel density, pupil diameter (PD) and iris thickness were measured in both the resting and drug-induced mydriasis states. Iris vessel density was measured by optical coherence tomography angiography (OCTA), PD was measured by a pupilometer, and iris thickness at the iris smooth muscle regions were measured using anterior segment optical coherence tomography (AS-OCT). RESULTS: The study included 34 pediatric T1DM patients and 50 adult T2DM patients, both groups without diabetic retinopathy, and age-sex-matched healthy controls. At baseline, T1DM children and healthy children showed no differences in iris blood flow, iris thickness, or PD. However, the adult T2DM group exhibited higher vessel density at the pupil margin, thinner iris thickness at the iris dilator region, and smaller PD compared to healthy adults, with these differences being statistically significant (P < 0.05). After pupil dilation, there were no changes in iris blood flow and PD in the T1DM group compared to healthy children, whereas the T2DM group showed a significantly smaller PD compared to healthy adults. Multivariate regression analysis revealed that in the T2DM group, glycated hemoglobin was an independent factor of PD after dilation (ß=-0.490, p = 0.031), with no such factors identified in the T1DM group. CONCLUSION: The insufficiently dilated pupil diameter after drug-induced mydriasis is correlated to the level of glycated hemoglobin among T2DM patients. TRIAL REGISTRATION: The registration number on the clinical trial website was NCT03631108.

Three-Year Follow-Up Study Investigating Changes in Retinal Vascular Morphology and the Relationship with Diabetic Retinopathy in Children with Type 1 Diabetes Mellitus.

INTRODUCTION: This study aimed to investigate changes in retinal microvascular morphology and associated factors, and their relationship with diabetic retinopathy (DR) in children with type 1 diabetes mellitus (T1DM). METHODS: Thirty-eight children enrolled in this 3-year follow-up study underwent complete ophthalmic examinations including fundus photography. Retinal vascular parameters were measured automatically and compared between baseline and follow-up. Multiple linear regression was used to investigate factors affecting changes in vascular parameters. Binary logistic regression was used to analyze the relationship between retinal microvascular morphology and DR. RESULTS: The caliber of all retinal vessels (within 1-1.5 papillary diameter [PD] from the center of the optic disc, p = 0.030; 1.5-2 PD, p = 0.003), arterioles, and venules (1.5-2 PD, p = 0.001) was narrower in nearly all regions in the follow-up group compared with the baseline group. Vascular tortuosity increased in the central part of the retina and decreased in the periphery. The density (1-1.5 PD, p = 0.030) and fractal dimension (p = 0.037) of retinal vessels were increased at the end of the follow-up compared with baseline. Retinal vascular caliber was independently correlated with DR (odds ratio 0.793 [95% confidence interval 0.633-0.993]; p = 0.044). CONCLUSION: Retinal microvascular morphology in children with T1DM varied with the disease course. Narrower retinal vessels may be an independent risk factor for DR. Results of this study emphasized the importance of regular follow-up of fundus vascular morphology for the detection of early DR in children with T1DM.

A 5-Year Clinical Experience of Pediatric Ophthalmic Ambulatory Surgery Under General Anesthesia From a Chinese Tertiary Children's Hospital.

PURPOSE: Ambulatory surgery (same-day or day surgery) is an efficient medical practice. However, there were few reports regarding the safety of ophthalmic ambulatory surgery for children under general anesthesia. This study aims to explore its clinical complications. DESIGN: A retrospective observational study. METHODS: The clinical data of pediatric patients who received ambulatory ophthalmic surgery under general anesthesia at the Children's Hospital of Fudan University from January 2015 to December 2019 were analyzed retrospectively. Postoperative complications, unplanned reoperation, delayed discharge, and other adverse events were analyzed. FINDINGS: Consecutive patients (N = 4,616) had an average age of 4.6 ± 2.6 years. The primary surgical procedures included chalazion incision and curettage (62.89%), strabismus surgery (18.98%), trichiasis surgery (14.36%), eyelid or orbital mass resection (2.49%), blepharoptosis surgery (0.91%), and other procedures (0.37%). The average operative time was 25.28 ± 20.45 minutes (n = 2,698), while the average length of hospital stay was 8.45 ± 2.61 hours. No serious adverse events or death happened. One case had delayed postoperative hemorrhage, one had a postoperative infection, and two had delayed discharge. The rate of unplanned reoperation was 0.39% 90 days after surgery, with recurrence of chalazion and postoperative complications of ptosis as the primary reasons. CONCLUSIONS: Pediatric ophthalmic ambulatory surgery under general anesthesia is a feasible and efficient operation mode with few complications for simple procedures with good general conditions. Further randomized controlled studies are needed to provide strong evidence of the safety and socioeconomic efficacy of this mode.

Metagenomic analysis of microbiological changes on the ocular surface of diabetic children and adolescents with a dry eye.

BACKGROUND: Microbiome changes on the ocular surface may cause dry eyes. A metagenome assay was used to compare the microbiome composition and function of the ocular surface between diabetic children and adolescents with dry eye, diabetic children and adolescents without dry eye, and normal children. MATERIALS AND METHODS: Twenty children and adolescents aged 8 to 16 with diabetes were selected from the Shanghai Children and Adolescent Diabetes Eye Study. Ten healthy children and adolescents belonging to the same age group were selected from the outpatient clinic during the same period. The participants were classified into the dry eye group (DM-DE group, n = 10), the non-dry eye group (DM-NDE group, n = 10) and the normal group (NDM group, n = 10). A conjunctival sac swab was collected for metagenomic sequencing, and the relationship between the microbiome composition and functional gene differences on the ocular surface with dry eye was studied. RESULTS: The classification composition and metabolic function of the microorganisms on the ocular surface of children in the 3 groups were analyzed. It was found that children's ocular microbiota was composed of bacteria, viruses and fungi. There were significant differences in α diversity and ß diversity of microbial composition of ocular surface between DM-DE group and NDM group(P<0.05). There were significant differences in α and ß diversity of metabolic pathways between the two groups(P<0.05). The functional pathways of ocular surface microorganisms in diabetic children with dry eyes were mainly derived from human disease, antibiotic resistance genes, carbohydrate, coenzyme and lipid transport and metabolism-related functional genes; In normal children, the functional pathways were mainly derived from replication, recombination, repair, signal transduction and defense-related functional genes. CONCLUSION: The DM-DE group have unique microbial composition and functional metabolic pathways. The dominant species and unique metabolic pathways of the ocular surface in the DM-DE group may be involved in the pathogenesis of dry eye in diabetic children.

OUTER RETINAL TUBULATION IN BIETTI CRYSTALLINE DYSTROPHY ASSOCIATED WITH THE RETINAL PIGMENT EPITHELIUM ATROPHY.

PURPOSE: To determine the prognostic value of outer retinal tubulation (ORT) in the eyes of a Chinese cohort with Bietti crystalline dystrophy (BCD). METHODS: This retrospective, multicenter cohort study enrolled 42 patients with clinically and genetically diagnosed BCD. Eighty eyes with good-quality images of spectral domain optical coherence tomography were included. Demographic details and clinical data were collected. The characteristics of ORT, including prevalence, location, and morphologic characteristics were analyzed. RESULTS: Forty-two patients with BCD harbored potentially CYP4V2 disease-causing mutations. The mutation spectrum comprised 17 unique variants, 9 of which were novel. Fifty-two of these 80 eyes demonstrated evidence of ORT. The incidence of ORT is significantly higher in Stage 2 than other stages ( P < 0.001). ORT was mainly bilateral and located at the margin of the atrophic area of retinal pigment epithelium (RPE), and dynamically changed with the progressive RPE atrophy. The process of RPE atrophy was slower in eyes with ORT ( P = 0.017), with significantly longer intact RPE width in Stage 3 ( P = 0.024). Eyes with ORT had slower vision loss than eyes without ORT ( P = 0.044). CONCLUSION: ORT may be a sign of the onset of RPE atrophy in early-stage BCD and may suggest less risk of rapid progression in late-stage BCD.

Is myopia accelerated in type 1 diabetes mellitus children? Analyses from the ocular parameters.

BACKGROUND: This study compares the ocular biometry with or without myopia in children with type 1 diabetes mellitus (T1DM) and healthy children in China to analyse the difference between myopia in T1DM and healthy children. METHODS: A case-control study was conducted at the Children's Hospital of Fudan University. The children were divided into four subgroups depending on myopia or non-myopia, T1DM or non-DM. The participants were evaluated for anterior chamber depth (ACD), lens thickness (LT), axial length (AL), average keratometry (K) and lens power (P). Furthermore, cycloplegic refraction was performed and the spherical equivalent (SE) was acquired. RESULTS: One hundred and ten patients with T1DM and 102 healthy subjects were included in this study. In the age-sex adjusted analysis, the myopia T1DM subgroup showed thicker LT (p = 0.001), larger P (p = 0.003) and similar ACD, AL, K and SE (all p > 0.05) compared to the myopia control subgroup. Additionally, the myopia T1DM subgroup showed longer AL (p < 0.001) and similar ACD, LT, K and P (all p > 0.05) as the non-myopia T1DM subgroup. In the multivariate linear regression, for T1DM patients, eyes with longer AL, shallower ACD, and larger P were associated with a decrease in SE (p < 0.001, p = 0.01, and p < 0.001, respectively). Meanwhile, for healthy controls, eyes with longer AL and larger P were associated with a decrease in SE (all p < 0.001). CONCLUSIONS: The ACD and LT of myopia T1DM children remained unchanged compared to non-myopia T1DM children. This means that the lens in the former group could not lose power as compensation for AL growth, thus providing evidence for the acceleration of myopia in T1DM children.

Discrepancies in Vessel Density and Blood Flow Distribution in Different Areas of the Iris among Pediatric Type 1 Diabetes Mellitus and Adult Type 2 Diabetes Mellitus Patients.

INTRODUCTION: Diabetes mellitus may compromise the vasculature of the iris, thereby leading to severe vision-threatening complications. This study aimed to investigate differences in iris blood flow indices between pediatric type 1 diabetes mellitus (T1DM) patients and adult type 2 diabetes mellitus (T2DM) patients. METHODS: This was a cross-sectional study. Pediatric T1DM patients and healthy children were members of the Shanghai Children and Adolescent Diabetes Eye (SCADE) cohort who visited Shanghai Eye Hospital in February 2022. The adult T2DM patients and healthy adults were patients who visited Shanghai General Hospital from October 2021 to January 2022. Iris OCTA was acquired through a Cirrus HD-OCT 5000 angiography system (Carl Zeiss Meditec, Inc.). A unique iris OCTA quantification method was used, and the vessel area density (VAD) and vessel skeleton density (VSD) were obtained. The area from the pupillary margin to the corneoscleral limbus was taken as the whole iris blood flow index, and the inner third near the pupillary margin of the whole iris was taken as the pupillary margin blood flow index. RESULTS: This study enrolled 34 pediatric T1DM patients, 34 age-matched healthy children, 34 adult T2DM patients, and 34 age-matched healthy adults. The whole iris and pupillary margin VAD and VSD of the pediatric T1DM patients were not different from those of healthy children. The whole iris VAD and VSD of the adult T2DM patients were lower than those of healthy adults, and the pupillary margin VAD and VSD were the same in these two groups. Compared with adult T2DM patients, pediatric T1DM patients had higher whole iris VAD and VSD and lower pupillary margin VAD and VSD values, all with statistical significance. Among diabetic patients, age, BMI, and glycated hemoglobin level were negative independent influencing factors for whole iris VAD and VSD, and age was a positive influencing factor for pupillary margin VAD and VSD. CONCLUSION: There are diverse alterations in iris vessel density and blood flow distribution between pediatric T1DM patients and adult T2DM patients.

Investigation of Potential Crucial Genes and Key Pathways in Keratoconus: An Analysis of Gene Expression Omnibus Data.

Keratoconus is one of the most common causes leading to visual impairment in young adult population. The pathogenesis of keratoconus remains poorly understood. The aim of this study was to identify the potential key genes and pathways associated with keratoconus and to further analyze its molecular mechanism. Two RNA-sequencing datasets of keratoconus and paired normal corneal tissues from the Gene Expression Omnibus database were obtained. Differentially expressed genes (DEGs) were identified, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. The protein-protein interaction (PPI) network of the DEGs was established, and the hub genes and significant gene modules of PPI were further constructed. Lastly, the GO and KEGG analyses of the hub gene were performed. In total, 548 common DEGs were identified. GO enrichment analysis showed that the DEGs were primarily associated with regulation of cell adhesion, the response to molecule of bacterial origin, lipopolysaccharide and biotic stimulus, collagen-containing extracellular matrix, extracellular matrix, and structure organization. KEGG pathway analysis showed that these DEGs were mainly involved in the TNF signaling pathway, IL-17 signaling pathway, Rheumatoid arthritis, Cytokine-cytokine receptor interaction. The PPI network was constructed with 146 nodes and 276 edges, and 3 significant modules are selected. Finally, top 10 hub genes were identified from the PPI network. The results revealed that extracellular matrix remodeling and immune inflammatory response could be the key links of keratoconus, TNF, IL6, IL1A, IL1B, CCL3, MMP3, MMP9, MMP1, and TGFB1 may be potential crucial genes, and TNF signaling pathway and IL-17 signaling pathway were the potential pathways accounting for pathogenesis and development of keratoconus.

Effects of high flow nasal cannula following minimally invasive esophagectomy in ICU patients: A prospective pre-post study.

BACKGROUND/PURPOSE: Patients with esophageal cancer who undergo minimally invasive esophagectomy are at risk of postoperative pulmonary complications. High-flow nasal cannula oxygen therapy delivers humidified, warmed positive airway pressure but has not been applied routinely after surgery. Here, we aimed to compare high-flow nasal cannula and conventional oxygen therapy in patients with esophageal cancer during intensive care unit hospitalization 48 h postoperatively. METHODS: In this prospective pre- and post-intervention study, patients with esophageal cancer who underwent elective minimally invasive esophagectomy (MIE) and were extubated in the operation room and admitted to the intensive care unit postoperatively were assigned to receive either high-flow nasal cannula (HFNCO) or standard oxygen (SO) therapy. Participants in the SO group were recruited before January 2020, and those in the HFNCO group were enrolled after January 2020. The primary outcome was the difference in postoperative pulmonary complication incidence. Secondary outcomes were the occurrence of desaturation within 48 h, PaO2/FiO2 within 48 h, anastomotic leakage, length of intensive care unit and hospital stay, and mortality. RESULTS: The standard oxygen and high-flow nasal cannula oxygen groups comprised 33 and 36 patients, respectively. Baseline characteristics were comparable between groups. In the HFNCO group, postoperative pulmonary complication incidence was significantly reduced (22.2% vs 45.5%) and PaO2/FiO2 was significantly increased. No other between-group differences were observed. CONCLUSION: HFNCO therapy significantly reduced postoperative pulmonary complication incidence after elective MIE in patients with esophageal cancer without increasing the risk of anastomotic leakage.

EGCG-coated silver nanoparticles self-assemble with selenium nanowires for treatment of drug-resistant bacterial infections by generating ROS and disrupting biofilms.

Bacterial infections pose a serious threat to human health, and the development of new antibiotics has not kept pace with the development of bacterial resistance. Therefore, there is an urgent need to design antibiotic-like nano-formulations that break through bacterial resistance mechanisms. In this work, we successfully synthesized a safe and effective antibacterial nano-formulation of Se@Ag@EGCG by self-assembly of epigallocatechin gallate (EGCG)-coated silver nanoparticles (Ag) on the surface of selenium nanowires (Se). Thein vitrobacteriostatic results showed that 40µg ml-1Se@Ag@EGCG had significant antibacterial activity against drug-resistantStaphylococcus aureus(S. aureus) andEscherichia coli(E. coli) by destroying the formation of bacterial biofilm, promoting the production of high concentration reactive oxygen species and destroying bacterial cell wall. In addition, the results ofin vivoantibacterial experiments showed that subcutaneous administration of 10 mg kg-1of Se@Ag@EGCG could promote wound healing by reducing apoptosis and inflammatory responses in infected wounds. It is worth mentioning that the reduced and modified Se@Ag@EGCG by this natural product has negligiblein vivotoxicity. This development strategy of nano-antibacterial materials, which breaks through the drug resistance mechanism, provides new ideas for the development of drugs for drug-resistant bacterial infections.

Axial length shortening after orthokeratology and its relationship with myopic control.

PURPOSE: To determine the pattern of axial variation in subjects with initial shortened axial length during the entire period of orthokeratology and to discuss the possibility of shortened AL after one month of orthokeratology becoming a predictor of myopia control. METHOD: This study retrospectively included 106 children with myopia aged 8 to 14 wearing OK lenses. Fifty-four eyes with shortened axial length (AL) at the first-month visit were enrolled in the axial length shortening (ALS) group, and fifty-two eyes without shortened AL were enrolled in the no axial length shortening (NALS) group. Axial length and refractive error at baseline and within the entire period of orthokeratology (20 months), including fitting, washout period and re-wear, were measured. Eighty-five children who started wearing single vision spectacle were also included as a control group. RESULTS: In the ALS group, AL became longer after shortening and slowly exceeded baseline; afterward, AL experienced a rebound during the washout period and shortened again if OK lenses were re-worn. After washout period, significant difference in AL (ALS:0.28 ± 0.19 mm, NALS: 0.52 ± 0.17 mm) and spherical equivalent (ALS:-0.43 ± 0.44D, NALS:-0.91 ± 0.40D) between the two groups were found(P<0.05). The changes in AL and SE were both significantly correlated with the changes in AL at the first-month visit (P<0.05). CONCLUSION: After AL is shortened in the initial stage of orthokeratology, it will experience a rapid rebound during the washout period, and the shortening can reappear when re-wearing OK lenses. Hence, the evaluation of orthokeratology will be more objective and accurate after the wash-out period. In addition, the existence and degree of axial shortening can be used as a predictor of long-term myopia development.

Directed evolution of the PobR allosteric transcription factor to generate a biosensor for 4-hydroxymandelic acid.

Hydroxy-mandelic acid (HMA) is widely applied in pharmaceuticals, food and cosmetics. In this study, we aimed to develop an allosteric transcription factors (aTFs) based biosensor for HMA. PobR, an aTF for HMA analog 4-hydroxybenzoic acid, was used to alter its selectivity and create novel aTFs responsive to HMA by directed evolution. We established a PobR mutant library with a capacity of 550,000 mutants using error-prone PCR and Megawhop PCR. Through our screening, two mutants were obtained with responsiveness to HMA. Analysis of each missense mutation indicating residues 122-126 were involved in its PobR ligand specificity. These results showed the effectiveness of directed evolution in switching the ligand specificity of a biosensor and improving HMA production.

Retinal vein occlusion with cerebral infarction in a preterm neonate: a case report.

BACKGROUND: Retinal vein occlusion (RVO) is a common disease that causes blindness in elderly patients, and cerebral infarction is also a severe disorder impairing the health of individuals. Both diseases are not common in neonates and are related to thrombosis. To date, only one case of simultaneous occurrence of RVO with intracranial haemorrhage in a full-term neonate has been reported. CASE PRESENTATION: A preterm neonate was diagnosed with cerebral infarction and RVO. Retinal haemorrhage and macular oedema were detected in the left eye after the onset of ipsilateral stroke. Although the retinal conditions in this case resolved spontaneously without ocular treatment, the long-term effect on visual function is still unknown. CONCLUSIONS: Given that ocular fundus examinations are rarely performed in paediatric stroke patients, a screening fundus examination in these newborns with stroke might be worth considering.

Compression Garments Reduce Soft Tissue Vibrations and Muscle Activations during Drop Jumps: An Accelerometry Evaluation.

OBJECTIVES: To explore the effects of wearing compression garments on joint mechanics, soft tissue vibration and muscle activities during drop jumps. METHODS: Twelve healthy male athletes were recruited to execute drop jumps from heights of 30, 45 and 60 cm whilst wearing compression shorts (CS) and control shorts (CON). Sagittal plane kinematics, ground reaction forces, accelerations of the quadriceps femoris (QF), hamstrings (HM) and shoe heel-cup, and electromyography images of the rectus femoris (RF) and biceps femoris (BF) were collected. RESULTS: Compared with wearing CON, wearing CS significantly reduced the QF peak acceleration at 45 and 60 cm and the HM peak acceleration at 30 cm. Wearing CS significantly increased the damping coefficient for QF and HM at 60 cm compared with wearing CON. Moreover, the peak transmissibility when wearing CS was significantly lower than that when wearing CON for all soft tissue compartments and heights, except for QF at 30 cm. Wearing CS reduced the RF activity during the pre-, post-, and eccentric activations for all heights and concentric activations at 45 cm; it also reduced the BF activity during post- and eccentric activations at 30 and 60 cm, respectively. The hip and knee joint moments and power or jump height were unaffected by the garment type. CONCLUSION: Applying external compression can reduce soft tissue vibrations without compromising neuromuscular performance during strenuous physical activities that involve exposure to impact-induced vibrations.

Melatonin regulates ATP content and fertilising capacity of Onychostoma macrolepis spermatozoa by inhibiting ROS accumulation during semen storage in vitro.

Melatonin (MLT) is an efficient antioxidant that protects spermatozoa against damages caused by oxidative stress. In this study, to maintain good function of Onychostoma macrolepis spermatozoa during semen preservation invitro at 4°C, different concentrations of MLT (0.5, 1 and 2µM) were added to the semen. After storage (0, 24, 48 and 72h), 1µM MLT in semen markedly improved sperm quality, as reflected by better plasma membrane integrity, the relative steady level of reactive oxygen species (ROS) and slower rate of decrease in mitochondrial membrane potential. Activated spermatozoa in semen with 1µM MLT had higher kinematic performance (i.e. percentage of motile and progressive spermatozoa and the beat cross frequency; P<0.05) and longer duration of sperm motility (P<0.05) compared with spermatozoa in semen withother MLT concentrations. Furthermore, 1µM MLT maintained higher ATP concentrations in spermatozoa during semen storage and significantly improved the fertilising capacity of spermatozoa after 72h semen storage compared with the other MLT concentrations. To expand wild resources of O. macrolepis, 1µM MLT can be used as a semen additive to maintain better sperm function and enhance sperm fertilising capacity in artificial insemination (AI).

Molecular characterisation of oestrogen receptor ERα and the effects of bisphenol A on its expression during sexual development in the Chinese giant salamander (Andrias davidianus).

The aim of this study was to characterise the molecular structure of the oestrogen receptor ERα and to evaluate the effect of bisphenol A (BPA) on ERα expression during sexual development of the Chinese giant salamander (Andrias davidianus). The ERα cDNA of A. davidianus includes an open reading frame of 1755bp (encoding 584 amino acids), a 219-bp 5' untranslated region (UTR) and a 611-bp 3'UTR. A polyadenylation signal was not found in the 3'UTR. Amino acid sequence analysis showed high homology between ERα of A. davidianus and that of other amphibians, such as Andrias japonicas (99.66% identity) and Rana rugose (81.06% identity). In 3-year-old A. davidianus, highest ERα expression was observed in the liver and gonads. During different developmental stages in A. davidianus (from 1 to 3 years of age), ERα expression in the testes increased gradually. ERα was localised in the epithelial cells of seminiferous lobules and in interstitial cells. ERα-positive cells were more abundant in the interstitial tissue during testicular development. ERα was located in the nucleus of oocytes during ovary development. We found that the sex of 6-month-old A. davidianus larvae could not be distinguished anatomically. The sex ratio did not change after larvae were treated with 10µM BPA for 1 month. However, BPA treatment reduced bodyweight and ERα expression in the gonads in male larvae.

Systematic analysis of the gerontome reveals links between aging and age-related diseases.

In model organisms, over 2,000 genes have been shown to modulate aging, the collection of which we call the 'gerontome'. Although some individual aging-related genes have been the subject of intense scrutiny, their analysis as a whole has been limited. In particular, the genetic interaction of aging and age-related pathologies remain a subject of debate. In this work, we perform a systematic analysis of the gerontome across species, including human aging-related genes. First, by classifying aging-related genes as pro- or anti-longevity, we define distinct pathways and genes that modulate aging in different ways. Our subsequent comparison of aging-related genes with age-related disease genes reveals species-specific effects with strong overlaps between aging and age-related diseases in mice, yet surprisingly few overlaps in lower model organisms. We discover that genetic links between aging and age-related diseases are due to a small fraction of aging-related genes which also tend to have a high network connectivity. Other insights from our systematic analysis include assessing how using datasets with genes more or less studied than average may result in biases, showing that age-related disease genes have faster molecular evolution rates and predicting new aging-related drugs based on drug-gene interaction data. Overall, this is the largest systems-level analysis of the genetics of aging to date and the first to discriminate anti- and pro-longevity genes, revealing new insights on aging-related genes as a whole and their interactions with age-related diseases.

Bacteria in Abnormal Eggs of Chinese Giant Salamanders (Andrias davidianus) May Derive from Gut.

Abnormal embryos of Chinese giant salamander (Andrias davidianus, CGS) were observed in an imitating ecologic breeding system at 20°C. The aim of the present study was to investigate the relationship of bacterial infection on the early embryonic development of CGS. The ratio of abnormal embryos at 10 days after embryos incubated was 35.0% ± 2.1%, 35.6% ± 2.3% and 34.7% ± 3.4% in six breeding system farms of Hanzhong city in the years 2014, 2015, and 2016, respectively. However, in the standard imitating ecology breeding mesocosm, the proportion of abnormal embryos was about 5%. Six bacteria species in the egg water of the early-dead embryos and eight bacteria species in the gut of healthy CGSs were detected and identified by PCR and 16S rRNA gene sequence homology analysis. All bacteria species in the egg water were also found in the cloaca contents. Cetobacterium somerae and Hafnia alvei, which individually can cause embryo death, were first isolated from egg water and gut of CGSs. Further, the egg jelly membrane and the egg water of embryos did not inhibit bacteria survival and the bacteria could individually lead to CGS larva death. These results suggest that bacteria in the eggs of CGS may derive from the gut and that high-velocity flow of water through nest may decrease bacterial infection of egg in the imitating ecologic culture system.

Flash visual evoked potentials are not specific enough to identify parieto-occipital lobe involvement in term neonates after significant hypoglycaemia.

AIM: Hypoglycaemia is a significant problem in high-risk neonates and predominant parieto-occipital lobe involvement has been observed after severe hypoglycaemic insult. We explored the use of flash visual evoked potentials (FVEP) in detecting parieto-occipital lobe involvement after significant hypoglycaemia. METHODS: Full-term neonates (n = 15) who underwent FVEP from January 2008 to May 2013 were compared with infants (n = 11) without hypoglycaemia or parietal-occipital lobe injury. Significant hypoglycaemia was defined as being symptomatic or needing steroids, glucagon or a glucose infusion rate of ≥12 mg/kg/min. RESULTS: The hypoglycaemia group exhibited delayed latency of the first positive waveform on FVEP. The initial detected time for hypoglycaemia was later in the eight subjects with seizures (median 51-h-old) than those without (median 22-h-old) (P = 0.003). Magnetic resonance imaging showed that 80% of the hypoglycaemia group exhibited occipital-lobe injuries, and they were more likely to exhibit abnormal FVEP morphology (P = 0.007) than the controls. FVEP exhibited 100% sensitivity, but only 25% specificity, for detecting injuries to the parieto-occipital lobes. CONCLUSION: Flash visual evoked potential (FVEP) was sensitive, but not sufficiently specific, in identifying parieto-occipital lobe injuries among term neonates exposed to significant hypoglycaemia. Larger studies exploring the potential role of FVEP in neonatal hypoglycaemia are required.