Intra-Anterior Chamber Injection of Ranibizumab in Advanced Pediatric Vitreoretinal Diseases.

Importance: Anti-vascular endothelial growth factor (VEGF) treatment through intravitreal or subretinal administrations has been proven effective for VEGF-driven pediatric vitreoretinal diseases but are not feasible for advanced cases, such as shallow traction retinal detachments or peripheral circumferential retinal detachments which adhere to the lens. Intra-anterior chamber injection (IAcI) of anti-VEGF may be a viable alternative in such cases but needs evaluation. Objective: To investigate the effects and safety of IAcI of anti-VEGF to treat VEGF-driven pediatric vitreoretinal diseases. Design, Setting, and Participants: This was a retrospective observational case series study conducted at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine in China. The study included 14 eyes of 13 children diagnosed with vitreoretinal disease exhibiting elevated vascular activity between January and August 2023. Intervention: IAcI with ranibizumab. Main Outcomes and Measures: Retinal vascular abnormalities, vitreous hemorrhage resolution, and complications 1 month and 3 months after injection. Results: Of 13 patients included in this study, 12 were male. The mean age was 4.6 years (range, 1 month to 9 years). Six patients were diagnosed with familial exudative vitreoretinopathy, 4 with morning glory syndrome, 1 with retinopathy of prematurity, and 2 with chronic retinal detachments of unknown causes. At 1-month postoperative follow-up, vascular activity had decreased in 14 of 14 eyes. At 3-month follow-up, vascular activity had resolved in 7 of 14 eyes, persisted in 6 of 14 eyes, and reactivated in 1 of 14 eyes. On final observation, no complications were reported. Conclusions and Relevance: These findings support the possibility of treatment using IAcI with ranibizumab to decrease retinal vascular abnormalities in familial exudative vitreoretinopathy or retinopathy of prematurity or related conditions, but further studies are needed to understand more precise benefits and risks. This approach might be considered in cases where intravitreal or subretinal injection are not feasible, recognizing the limitations of these findings and that longer-term outcomes still need to be monitored.

Prenatal diagnostic approaches diagnosed craniosynostosis and identified a novel nonsense variant in SMAD6 in a Chinese fetus.

Craniosynostosis is one of the most common congenital craniofacial birth defects. The genetic etiology is complex, involving syndromic developmental diseases, chromosomal abnormalities, and monogenic non-syndromic diseases. Herein, we presented a proband of craniosynostosis, who firstly displayed structural abnormalities. This research conducted dynamic ultrasound monitoring a fetus with gradually developing intrauterine growth retardation (IUGR). A novel de novo variant c.41G > A: p.W14* in SMAD6 was identified by pedigree analysis and genetic examination approaches. Recombinant plasmid carrying wild-type sequence and mutant that carries c.41G > A in SMAD6 were constructed and transfected into HEK293T cells. mRNA and protein expression of SMAD6 were reduced in SMAD6 mutants compared to the wild type. Cycloheximide (CHX) treatment and si-UPF1 transfection rescued the SMAD6 mRNA expression in the mutant construct, indicating that c.41G > A: p.W14* in SMAD6 triggered nonsense-mediated mRNA degradation (NMD) process and thus led to haploinsufficiency of the protein product. Our study demonstrated that whole-exome sequencing (WES) was a powerful tool for further diagnosis and etiological identification once fetal malformation was detected by ultrasound. Novel de novo c.41G > A: p.W14* in SMAD6 is pathogenic and potentially leads to craniosynostosis via NMD process.

Single-cell and spatial transcriptomics reveal POSTN+ cancer-associated fibroblasts correlated with immune suppression and tumour progression in non-small cell lung cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are potential targets for cancer therapy. Due to the heterogeneity of CAFs, the influence of CAF subpopulations on the progression of lung cancer is still unclear, which impedes the translational advances in targeting CAFs. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on tumour, paired tumour-adjacent, and normal samples from 16 non-small cell lung cancer (NSCLC) patients. CAF subpopulations were analyzed after integration with published NSCLC scRNA-seq data. SpaTial enhanced resolution omics-sequencing (Stereo-seq) was applied in tumour and tumour-adjacent samples from seven NSCLC patients to map the architecture of major cell populations in tumour microenvironment (TME). Immunohistochemistry (IHC) and multiplexed IHC (mIHC) were used to validate marker gene expression and the association of CAFs with immune infiltration in TME. RESULTS: A subcluster of myofibroblastic CAFs, POSTN+ CAFs, were significantly enriched in advanced tumours and presented gene expression signatures related to extracellular matrix remodeling, tumour invasion pathways and immune suppression. Stereo-seq and mIHC demonstrated that POSTN+ CAFs were in close localization with SPP1+ macrophages and were associated with the exhausted phenotype and lower infiltration of T cells. POSTN expression or the abundance of POSTN+ CAFs were associated with poor prognosis of NSCLC. CONCLUSIONS: Our study identified a myofibroblastic CAF subpopulation, POSTN+ CAFs, which might associate with SPP1+ macrophages to promote the formation of desmoplastic architecture and participate in immune suppression. Furthermore, we showed that POSTN+ CAFs associated with cancer progression and poor clinical outcomes and may provide new insights on the treatment of NSCLC.

Retinal Damage After Repeated Low-level Red-Light Laser Exposure.

This case report discusses retinal damage incurred after repeated low-level red-light laser exposure in a 12-year-old female patient with a history of myopia.

A hybrid method of frequency-weighted energy operator and power spectrum fusion to detect bearing faults.

The difficulties in early fault diagnosis of bearings mainly include two aspects: first, the initial damage size of the bearing is small, and the abnormal vibration caused by slight damage to the bearing is very weak. Second, vibration signals collected in actual industrial environments always contain strong noise interference. Therefore, traditional diagnostic procedures are not satisfactory. To address these challenges, this work provides a hybrid model combining frequency-weighted energy operator (FWEO) with power spectrum fusion (PSF) to identify weak fault features of bearings and detect different fault types. Different from traditional time-domain signal filtering, PSF is first used to reduce the interference of noise components in the power spectrum, which will not weaken the fault signal components during denoising. Second, the filtered signal is transformed into the time domain and FWEO is employed to further enhance the cyclic fault signal caused by the weak defect of the bearing. Finally, the existence of a fault is identified by observing the squared envelope spectrum of the signal. The effectiveness of the proposed hybrid model is demonstrated through two simulated fault signals and three different experimental fault signals. The results show that the proposed model has high anti-noise performance and robustness and can extract the fault frequency well.

Mueller matrix imaging of pathological slides with plastic coverslips.

Mueller matrix microscopy is capable of polarization characterization of pathological samples and polarization imaging based digital pathology. In recent years, hospitals are replacing glass coverslips with plastic coverslips for automatic preparations of dry and clean pathological slides with less slide-sticking and air bubbles. However, plastic coverslips are usually birefringent and introduce polarization artifacts in Mueller matrix imaging. In this study, a spatial frequency based calibration method (SFCM) is used to remove such polarization artifacts. The polarization information of the plastic coverslips and the pathological tissues are separated by the spatial frequency analysis, then the Mueller matrix images of pathological tissues are restored by matrix inversions. By cutting two adjacent lung cancer tissue slides, we prepare paired samples of very similar pathological structures but one with a glass coverslip and the other with a plastic coverslip. Comparisons between Mueller matrix images of the paired samples show that SFCM can effectively remove the artifacts due to plastic coverslip.

Associations of MTHFR Polymorphisms and Cytosine Modifications with Early-Gestational Diabetes Mellitus in Chinese Pregnant Women.

Early-Gestational Diabetes Mellitus (Early-GDM) is a complex condition that may cause complications in infants of affected mothers. The aim of this case-control study was to analyze the effects of genetic-epigenetic interaction on Early-GDM and fetal development with respect to cytosine modifications (i.e., 5mC, 5-methylcytosines; and 5hmC, 5-hydroxymethylcytosines) and single nucleotide polymorphisms (SNPs) of MTHFR, a key gene involving cytosine modifications. Peripheral blood samples were collected from 92 women in their first or second trimester of pregnancy (Early-GDM, n = 14; Controls, n = 78). Global DNA 5mC and 5hmC were quantified by HPLC-MS/MS, and MTHFR SNPs (rs1801133 C > T and rs1801131 A > C) were determined by TaqMan-qPCR. Association analysis suggested that MTHFR rs1801133 TT genotype was a risk factor of Early-GDM (OR [odds ratio] = 4.00; 95% CI [confidence interval]: 1.24, 12.86; p = 0.02). The C allele of rs1801131 appeared to be a protective factor for the 2-h OGTT (oral glucose tolerance test) (OR = -0.79; 95% CI: -1.48, -0.10; p = 0.03). Patients with Early-GDM had higher global 5mC and lower global 5hmC. The reduction of global 5hmC and the TT genotype of rs1801133 were associated with higher level of the 1st-FBG (fasting blood glucose in the first trimester) (p < 0.05). Additionally, global 5mC showed a positive correlation with birth weight, body length and head circumference of newborns, while global 5hmC showed a negative correlation with birth weight. The current study implicated MTHFR SNPs and cytosine modifications in the development of Early-GDM and potential complications in their newborns.

T-type cell mediated photoacoustic spectroscopy for simultaneous detection of multi-component gases based on triple resonance modality.

Enhancing multi-gas detectability using photoacoustic spectroscopy capable of simultaneous detection, highly selectivity and less cross-interference is essential for dissolved gas sensing application. A T-type photoacoustic cell was designed and verified to be an appropriate sensor, due to the resonant frequencies of which are determined jointly by absorption and resonant cylinders. The three designated resonance modes were investigated from both simulation and experiments to present the comparable amplitude responses by introducing excitation beam position optimization. The capability of multi-gas detection was demonstrated by measuring CO, CH4 and C2H2 simultaneously using QCL, ICL and DFB lasers as excitation sources respectively. The influence of potential cross-sensitivity towards humidity have been examined in terms of multi-gas detection. The experimentally determined minimum detection limits of CO, CH4 and C2H2 were 89ppb, 80ppb and 664ppb respectively, corresponding to the normalized noise equivalent absorption coefficients of 5.75 × 10-7 cm-1 W Hz-1/2, 1.97 × 10-8 cm-1 W Hz-1/2 and 4.23 × 10-8 cm-1 W Hz-1/2.

Delayed Doublet Emission in a Cerium(III) Complex.

Doublet emission from open-shell molecules has demonstrated its research and application value in recent years. However, understandings of the photoluminescence mechanism of open-shell molecules are far less than that of closed-shell molecules, leading to challenges in molecular design of efficient doublet emission systems. Here we report a cerium(III) 4-(9H-carbozol-9-yl)phenyl-tris(pyrazolyl)borate complex Ce(CzPhTp)3 with a new luminescence mechanism of delayed doublet emission, which also represents the first example with metal-centered delayed photoluminescence. The energy gap between the doublet and triplet excited states of Ce(CzPhTp)3 is reduced by the management of the inner and outer coordination spheres, thereby promoting efficient energy transfer between the two excited states and activating the delayed emission. The photoluminescence mechanism discovered may provide a new way for the design of efficient doublet emission and bring insights into rational molecular design and energy level regulation in open-shell molecules.

Comprehensive single-cell transcriptomic and proteomic analysis reveals NK cell exhaustion and unique tumor cell evolutionary trajectory in non-keratinizing nasopharyngeal carcinoma.

BACKGROUND: Nonkeratinizing nasopharyngeal carcinoma (NK-NPC) has a strong association with Epstein-Barr virus (EBV) infection. The role of NK cells and the tumor cell evolutionary trajectory in NK-NPC remain unclear. In this study, we aim to investigate the function of NK cell and the evolutionary trajectory of tumor cells in NK-NPC by single-cell transcriptomic analysis, proteomics and immunohistochemistry. METHODS: NK-NPC (n = 3) and normal nasopharyngeal mucosa cases (n = 3) were collected for proteomic analysis. Single-cell transcriptomic data of NK-NPC (n = 10) and nasopharyngeal lymphatic hyperplasia (NLH, n = 3) were obtained from Gene Expression Omnibus (GSE162025 and GSE150825). Quality control, dimension reduction and clustering were based on Seurat software (v4.0.2) process and batch effects were removed by harmony (v0.1.1) software. Normal cells of nasopharyngeal mucosa and tumor cells of NK-NPC were identified using copykat software (v1.0.8). Cell-cell interactions were explored using CellChat software (v1.4.0). Tumor cell evolutionary trajectory analysis was performed using SCORPIUS software (v1.0.8). Protein and gene function enrichment analyses were performed using clusterProfiler software (v4.2.2). RESULTS: A total of 161 differentially expressed proteins were obtained between NK-NPC (n = 3) and normal nasopharyngeal mucosa (n = 3) by proteomics (log2 fold change > 0.5 and P value < 0.05). Most of proteins associated with the nature killer cell mediated cytotoxicity pathway were downregulated in the NK-NPC group. In single cell transcriptomics, we identified three NK cell subsets (NK1-3), among which NK cell exhaustion was identified in the NK3 subset with high ZNF683 expression (a signature of tissue-resident NK cell) in NK-NPC. We demonstrated the presence of this ZNF683 + NK cell subset in NK-NPC but not in NLH. We also performed immunohistochemical experiments with TIGIT and LAG3 to confirm NK cell exhaustion in NK-NPC. Moreover, the trajectory analysis revealed that the evolutionary trajectory of NK-NPC tumor cells was associated with the status of EBV infection (active or latent). The analysis of cell-cell interactions uncovered a complex network of cellular interactions in NK-NPC. CONCLUSIONS: This study revealed that the NK cell exhaustion might be induced by upregulation of inhibitory receptors on the surface of NK cells in NK-NPC. Treatments for the reversal of NK cell exhaustion may be a promising strategy for NK-NPC. Meanwhile, we identified a unique evolutionary trajectory of tumor cells with active status of EBV-infection in NK-NPC for the first time. Our study may provide new immunotherapeutic targets and new sight of evolutionary trajectory involving tumor genesis, development and metastasis in NK-NPC.

Warm-White-Light Perdeuterated Dy(III) Complex with a Photoluminescence Quantum Yield of up to 72% in Deuterated Chloroform.

Herein, a deuteration strategy is proposed to enhance the photoluminescence quantum yield (PLQY) of a Dy(III) complex. The perdeuterated Dy(III) complex Dy(D-DPPOP)3 (D-DPPOP = 6-[bis(phenyl-d5)phosphoryl]picolinate-d3) exhibits a high PLQY of up to 72% in deuterated chloroform, which is 4.8 times higher than that of the nondeuterated Dy(III) complex Dy(DPPOP)3. Then the corresponding ultraviolet-excited light-emitting diode is fabricated, showing a warm-white light with a Commission Internationale de l'Eclairage (CIE) of (0.36, 0.41) and a color temperature of around 4800 K. The deuteration strategy to improve the PLQY of the Dy(III) complex is proved in this work, and it will inspire the further design of white-emission Dy(III) complexes with high efficiency.

Establishment and validation of a predictive nomogram for gestational diabetes mellitus during early pregnancy term: A retrospective study.

Objective: This study aims to develop and evaluate a predictive nomogram for early assessment risk factors of gestational diabetes mellitus (GDM) during early pregnancy term, so as to help early clinical management and intervention. Methods: A total of 824 pregnant women at Zhongnan Hospital of Wuhan University and Maternal and Child Health Hospital of Hubei Province from 1 February 2020 to 30 April 2020 were enrolled in a retrospective observational study and comprised the training dataset. Routine clinical and laboratory information was collected; we applied least absolute shrinkage and selection operator (LASSO) logistic regression and multivariate ROC risk analysis to determine significant predictors and establish the nomogram, and the early pregnancy files (gestational weeks 12-16, n = 392) at the same hospital were collected as a validation dataset. We evaluated the nomogram via the receiver operating characteristic (ROC) curve, C-index, calibration curve, and decision curve analysis (DCA). Results: We conducted LASSO analysis and multivariate regression to establish a GDM nomogram during the early pregnancy term; the five selected risk predictors are as follows: age, blood urea nitrogen (BUN), fibrinogen-to-albumin ratio (FAR), blood urea nitrogen-to-creatinine ratio (BUN/Cr), and blood urea nitrogen-to-albumin ratio (BUN/ALB). The calibration curve and DCA present optimal predictive power. DCA demonstrates that the nomogram could be applied clinically. Conclusion: An effective nomogram that predicts GDM should be established in order to help clinical management and intervention at the early gestational stage.

IgG4-related disease with kidney and lymph nodes involvement: a case-based review.

IgG4-related disease (IgG4-RD), a rare immune-mediated chronic fibro-inflammatory condition, has various initial symptoms, thus posing diagnostic and therapeutic challenges. Here, we report a case of IgG4-RD in a 35-year-old man with initial clinical symptoms of facial edema and recent onset of proteinuria. It took more than 1 year from the onset of clinical symptoms to diagnosis. Pathological examination of renal biopsy revealed significant renal interstitial lymphoid tissue hyperplasia simulating growth pattern of lymphoma. Immunohistochemical (IHC) staining results showed that CD4 + T lymphocyte hyperplasia was dominant. There was no significant deletion of CD2/CD3/CD5/CD7. No monoclone was detected in TCR gene rearrangement. IHC staining showed that the number of IgG4-positive cells was greater than 100/HPF. The ratio of IgG4/IgG was greater than 40%. Combined with clinically examinations, IgG4-related tubulointerstitial nephritis was considered. Further cervical lymph node biopsy results suggested IgG4-related lymphadenopathy. He received methylprednisolone 40 mg/day intravenously for 10 days, leading to normal results of laboratory tests and clinical manifestations. The patient had a good prognosis without recurrence during 14 months of follow-up. This case report can be used as a reference for early diagnosis and treatment of such patients in the future.

Enhancement of Visible-Light-Driven Hydrogen Evolution Activity of 2D π-Conjugated Bipyridine-Based Covalent Organic Frameworks via Post-Protonation.

Photocatalytic hydrogen (H2 ) evolution represents a promising and sustainable technology. Covalent organic frameworks (COFs)-based photocatalysts have received growing attention. A 2D fully conjugated ethylene-linked COF (BTT-BPy-COF) was fabricated with a dedicated designed active site. The introduced bipyridine sites enable a facile post-protonation strategy to fine-tune the actives sites, which results in a largely improved charge-separation efficiency and increased hydrophilicity in the pore channels synergically. After modulating the degree of protonation, the optimal BTT-BPy-PCOF exhibits a remarkable H2 evolution rate of 15.8 mmol g-1 h-1 under visible light, which surpasses the biphenyl-based COF 6 times. By using different types of acids, the post-protonation is proved to be a potential universal strategy for promoting photocatalytic H2 evolution. This strategy would provide important guidance for the design of highly efficient organic semiconductor photocatalysts.

4f → 3d sensitization: a luminescent EuII-MnII heteronuclear complex with a near-unity quantum yield.

A new heteronuclear EuII-MnII complex [Eu(N2O6)]MnBr4 (N2O6 = 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) is designed and synthesized, which shows an intense green emission from MnII with a near-unity photoluminescence quantum yield. Measurement of excited-state dynamics demonstrated the sensitization process from EuII to MnII, which represents the first example of f → d molecular sensitization. Due to the large optical absorption cross-section of the EuII center, [Eu(N2O6)]MnBr4 shows an emission intensity 7 to 2500 times stronger than that of the SrII-MnII control complex [Sr(N2O6)]MnBr4 upon the excitation of near ultraviolet to blue light.

Shift work and nonalcoholic fatty liver disease incidence among Chinese rail workers: a 4-year longitudinal cohort study.

PURPOSE: Occupational harmful factors, such as shift work, are attracting increasing attention as a potential cause of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to identify the association between shift work and NAFLD incidence in Chinese rail population. METHODS: A cohort study was conducted among 14,112 rail workers for 4-year follow-up. Shift work frequency and other potential variables were recorded by questionnaires, including demographic, lifestyle, and occupation information. Besides, body mass index, blood pressure, fasting blood glucose, total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase were measured by anthropometric measurement and blood test. Diagnosis of new NAFLD case was based on abdominal ultrasonography. Cox proportional hazards regression model was used to determine whether shift work has effect on occurrence of NAFLD. RESULTS: The incidence of NAFLD was 30.43% in total subjects. After adjustment for possible confounders, the RRs of NAFLD were 1.069 (95% CI 0.998-1.146) and 1.179 (95% CI 1.059-1.312) in occasionally shift work group and frequently shift work group respectively, compared to the seldom shift work group. In stratified analyses, the RRs of NAFLD incidence linked to shift work exposure seems increase among female and elder. The results of three sensitivity analyses were similar with main analysis. CONCLUSIONS: This research provided further evidence of positive harmful effect of shift work on NAFLD incidence in Chinese rail workers, particularly in frequently shift work population. The risk estimate of shift work on NAFLD was higher in female and elder.

A Decision Probability Transformation Method Based on the Neural Network.

When the Dempster-Shafer evidence theory is applied to the field of information fusion, how to reasonably transform the basic probability assignment (BPA) into probability to improve decision-making efficiency has been a key challenge. To address this challenge, this paper proposes an efficient probability transformation method based on neural network to achieve the transformation from the BPA to the probabilistic decision. First, a neural network is constructed based on the BPA of propositions in the mass function. Next, the average information content and the interval information content are used to quantify the information contained in each proposition subset and combined to construct the weighting function with parameter r. Then, the BPA of the input layer and the bias units are allocated to the proposition subset in each hidden layer according to the weight factors until the probability of each single-element proposition with the variable is output. Finally, the parameter r and the optimal transform results are obtained under the premise of maximizing the probabilistic information content. The proposed method satisfies the consistency of the upper and lower boundaries of each proposition. Extensive examples and a practical application show that, compared with the other methods, the proposed method not only has higher applicability, but also has lower uncertainty regarding the transformation result information.