Preclinical 3D model screening reveals digoxin as an effective therapy for a rare and aggressive type of endometrial cancer.

OBJECTIVE: Dedifferentiated endometrial carcinoma (DDEC) characterized by SWItch/Sucrose Non-Fermentable (SWI/SNF) complex inactivation is a highly aggressive type of endometrial cancer without effective systemic therapy options. Its uncommon nature and aggressive disease trajectory pose significant challenges for therapeutic progress. To address this obstacle, we focused on developing preclinical models tailored to this tumor type and established patient tumor-derived three-dimensional (3D) spheroid models of DDEC. METHODS: High-throughput drug repurposing screens were performed on in vitro 3D spheroid models of DDEC cell lines (SMARCA4-inactivated DDEC-1 and ARID1A/ARID1B co-inactivated DDEC-2). The dose-response relationships of the identified candidate drugs were evaluated in vitro, followed by in vivo evaluation using xenograft models of DDEC-1 and DDEC-2. RESULTS: Drug screen in 3D models identified multiple cardiac glycosides including digoxin and digitoxin as candidate drugs in both DDEC-1 and DDEC-2. Subsequent in vitro dose-response analyses confirmed the inhibitory activity of digoxin and digitoxin with both drugs showing lower IC50 in DDEC cells compared to non-DDEC endometrial cancer cells. In in vivo xenograft models, digoxin significantly suppressed the growth of DDEC tumors at clinically relevant serum concentrations. CONCLUSION: Using biologically precise preclinical models of DDEC derived from patient tumor samples, our study identified digoxin as an effective drug in suppressing DDEC tumor growth. These findings provide compelling preclinical evidence for the use of digoxin as systemic therapy for SWI/SNF-inactivated DDEC, which may also be applicable to other SWI/SNF-inactivated tumor types.

Evaluation of combined epiretinal membrane removal with intravitreal triamcinolone injection utilizing ectopic inner foveal layer staging scheme.

OBJECTIVE: To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme. METHODS: Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups. RESULTS: After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10). CONCLUSION: Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM.

Upregulation of Formaldehyde in Parkinson's Disease Found by a Near-Infrared Lysosome-Targeted Fluorescent Probe.

Parkinson's disease (PD) is one of the major neurodegenerative diseases caused by complex pathological processes. As a signal molecule, formaldehyde is closely linked to nervous systems, but the relationship between PD and formaldehyde levels remains largely unclear. We speculated that formaldehyde might be a potential biomarker for PD. To prove it, we constructed the first near-infrared (NIR) lysosome-targeted formaldehyde fluorescent probe (named NIR-Lyso-FA) to explore the relationship between formaldehyde and PD. The novel fluorescent probe achieves formaldehyde detection in vitro and in vivo, thanks to its excellent properties such as NIR emission, large Stokes shift, and fast response to formaldehyde. Crucially, utilizing the novel probe NIR-Lyso-FA, formaldehyde overexpression was discovered for the first time in cellular, zebrafish, and mouse PD models, supporting our guess that formaldehyde can function as a possible biomarker for PD. We anticipate that this finding will offer insightful information for PD pathophysiology, diagnosis, medication development, and treatment.

Establishment and validation of preclinical models of SMARCA4-inactivated and ARID1A/ARID1B co-inactivated dedifferentiated endometrial carcinoma.

OBJECTIVE: Dedifferentiated endometrial cancer (DDEC) is an uncommon and clinically highly aggressive subtype of endometrial cancer characterized by genomic inactivation of SWItch/Sucrose Non-Fermentable (SWI/SNF) complex protein. It responds poorly to conventional systemic treatment and its rapidly progressive clinical course limits the therapeutic windows to trial additional lines of therapies. This underscores a pressing need for biologically accurate preclinical tumor models to accelerate therapeutic development. METHODS: DDEC tumor from surgical samples were implanted into immunocompromised mice for patient-derived xenograft (PDX) and cell line development. The histologic, immunophenotypic, genetic and epigenetic features of the patient tumors and the established PDX models were characterized. The SMARCA4-deficienct DDEC model was evaluated for its sensitivity toward a KDM6A/B inhibitor (GSK-J4) that was previously reported to be effective therapy for other SMARCA4-deficient cancer types. RESULTS: All three DDEC models exhibited rapid growth in vitro and in vivo, with two PDX models showing spontaneous development of metastases in vivo. The PDX tumors maintained the same undifferentiated histology and immunophenotype, and exhibited identical genomic and methylation profiles as seen in the respective parental tumors, including a mismatch repair (MMR)-deficient DDEC with genomic inactivation of SMARCA4, and two MMR-deficient DDECs with genomic inactivation of both ARID1A and ARID1B. Although the SMARCA4-deficient cell line showed low micromolecular sensitivity to GSK-J4, no significant tumor growth inhibition was observed in the corresponding PDX model. CONCLUSIONS: These established patient tumor-derived models accurately depict DDEC and represent valuable preclinical tools to gain therapeutic insights into this aggressive tumor type.

Evaluation and comparison of ocular biometric parameters obtained with Tomey OA-2000 in silicone oil-filled aphakic eyes.

PURPOSE: To evaluate a new non-contact instrument (OA-2000) measuring the ocular biometry parameters of silicone oil (SO)-filled aphakic eyes, as compared with IOLMaster 700. METHODS: Forty SO-filled aphakic eyes of 40 patients were enrolled in this cross-sectional clinical trial. The axial length (AL), central corneal thickness (CCT), keratometry ((flattest keratometry) Kf and (steep keratometry, 90° apart from Kf) Ks), and axis of the Kf (Ax1) were measured with OA-2000 and IOLMaster 700. The coefficient of variation (CoV) was calculated to assess the repeatability. The correlation was evaluated by the Pearson coefficient. Bland-Altman analysis and paired t test were used to analyze the agreements and differences of parameters measured by the two devices, respectively. RESULTS: The mean AL obtained with the OA-2000 was 23.57 ± 0.93 mm (range: 21.50 to 25.68 mm), and that obtained with the IOLMaster 700 was 23.69 ± 0.94 mm (range: 21.85 to 25.86 mm), resulting in a mean offset of 0.124 ± 0.125 mm (p < 0.001). The mean offset of CCT measured by OA-2000 and IOLMaster 700 was 14.6 ± 7.5 µm (p < 0.001). However, the Kf, Ks and Ax1 values from the two devices were comparable (p > 0.05). All the measured parameters of the two devices showed strong linear correlations (all r ≥ 0.966). The Bland-Altman analysis showed a narrow 95% limits of agreement (LoA) of Kf, Ks and AL, but 95%LoA of CCT and Ax1 was wide, which were - 29.3 ~ 0.1 µm and-25.9 ~ 30.7°respectively. The CoVs of the biometric parameters obtained with OA-2000 were lower than 1%. CONCLUSION: In SO-filled aphakic eyes, the ocular parameters (including AL, Kf, Ks, Ax1, and CCT) measured by the OA-2000 and IOLMaster 700 had a good correlation. Two devices had an excellent agreement on ocular biometric measurements of Kf, Ks and AL. The OA-2000 provided excellent repeatability of ocular parameters in SO-filled aphakic eyes.

Effects of vitamin C combined with rbFGF on inflammatory factors and oxygen environment in patients with high-voltage electrical burns.

To investigate the effect of vitamin C combined with recombinant basic fibroblast growth factor (rbFGF) on inflammatory factors and oxygen environment in patients with high-voltage electrical burns. A retrospective analysis of 98 patients with high-voltage electrical burns admitted to our hospital from January 2021 to April 2022. A total of 98 patients were divided into research group and control group, including 49 cases treated with vitamin C combined with rbFGF and 49 cases treated with only rbFGF. The disappearance time of clinical symptoms, wound healing rate, area of granulation tissue growth, level of inflammatory factors, oxygen environment were compared between two groups after one and three courses of treatment. After treatment, the disappearance time of erythema, pain, swelling, blisters, exudate symptoms, wound healing time, scab formation time, and hospitalisation time in the research group were significantly better than those in control group (P < .05). There was no significant difference in the wound healing rate and area of granulation tissue growth between the two groups after one course of treatment (P > .05), while it is significantly better than those in control group after three courses of treatment (P < .05). The inflammatory factors, succinate dehydrogenase (SDH), lactate dehydrogenase (LDH) scores in research group were significantly better than that in control group after three courses of treatment (P < .05). Vitamin C combined with rbFGF may be worthy to reduce inflammatory factors, regulate oxygen environment, which can be popularised and applied in clinical practice.

Surface Curvature Dominated Guest-Induced Nonequilibrium Deformations of Single Covalent Organic Framework-300 Particles.

Understanding the guest-induced dynamic deformation process of covalent organic frameworks (COFs) is vitally important to further increase their stimulus-response performances. Here we report on the dark-field microscopic (DFM) imaging approach to in situ monitor the guest-induced deformation evolution of individual COF-300 crystals in real time. We observe not only transient and nonequilibrium intermediate deformation states but also local surface curvature-driven diverse adsorption behaviours of single COF-300 particles for dichloromethane (DCM), undergoing one, two, and multiple expansion-contraction deformations as well as contraction-to-expansion transition. The surface curvature-dominated deformations are ascribed to the significant differences in the adsorption capacity for DCM at the curved tip and flat side regions, in which DCM can be adsorbed preferentially by curved tip regions of COF-300.

A Magnetically Driven Tandem Chip Enables Rapid Isolation and Multiplexed Profiling of Extracellular Vesicles.

The protein phenotypes of extracellular vesicles (EVs) have emerged as promising biomarkers for cancer diagnosis and treatment monitoring. However, the technical challenges in rapid isolation and multiplexed molecular detection of EVs have limited their clinical practice. Herein, we developed a magnetically driven tandem chip to achieve streamlined rapid isolation and multiplexed profiling of surface protein biomarkers of EVs. Driven by magnetic force, the magnetic nanomixers not only act as tiny stir bars to promote mass transfer and enhance reaction efficiency of EVs, but also transport on communicating vessels of the tandem chip continuously and expedite the assay workflow. We designed cyclic surface enhancement of Raman scattering (SERS) tags to bind with target EVs and then release them by exonuclease I, eliminating steric hindrance and amplifying the SERS signal of multiple protein biomarkers on EVs. Due to the excellent assay performance, six breast cancer biomarkers were detected simultaneously on EVs using only 10 µL plasma within 1.5 h. The unweighted SUM signature offers great accuracy in discriminating breast cancer patients from healthy donors. Overall, the dynamic magnetic driving tandem chip offers a new avenue to advance the clinical application of EV-based liquid biopsy.

COMPARISON OF INTERNAL LIMITING MEMBRANE PEELING WITH THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR RHEGMATOGENOUS RETINAL DETACHMENT COEXISTING WITH MACULAR HOLE.

PURPOSE: To evaluate the anatomical and functional outcomes of internal limiting membrane (ILM) peeling and the inverted ILM flap technique for rhegmatogenous retinal detachment coexisting with macular hole. METHODS: This retrospective study evaluated the medical records of 79 eyes with concurrent rhegmatogenous retinal detachment and macular hole received vitrectomy and silicone oil tamponade, with ILM peeling on 56 eyes and the inverted ILM flap technique on 23 eyes. RESULTS: The Type 1 closure rate was greater in the inverted ILM flap group than the ILM peeling group (82.6% vs. 55.4%, P = 0.038). Lines of improvement were 7.8 ± 5.3 in the ILM peeling group and 8.9 ± 5.6 in the inverted ILM flap group. Postoperative epiretinal membrane and retinal reattachment rates were similar in two surgical groups (16.1% vs. 21.7%, P = 0.535 and 94.6% vs. 95.7%, P = 0.999, respectively). Type 1 closure was significantly correlated with the inverted ILM flap technique (OR = 5.568, P = 0.023). The inverted ILM flap technique showed no significant association with the final logarithm of the minimum angle of resolution best-corrected visual acuity in multivariate model analysis. CONCLUSION: The inverted ILM flap technique was more effective in restoring the macular structure in patients with rhegmatogenous retinal detachment and coexisting macular hole, but the functional outcomes of the two strategies were comparable.

Diabetic retinopathy with extensively large area of capillary non-perfusion: characteristics and treatment outcomes.

BACKGROUND: Capillary non-perfusion is an important characteristic for diabetic retinopathy (DR) indicating microvascular damage and ischemia. Data on the description and treatment outcomes of DR with large area of non-perfusion are lacking to date. We aim to describe the characteristics and treatment outcomes in a series of patients with DR who presented extensively large area of capillary non-perfusion (LACNP). METHODS: Fundus fluorescein angiograms from medical charts in patients diagnosed with DR between Jan 2017 and Dec 2019 were retrospectively reviewed. Clinical data in eyes with LACNP including imaging and laboratory findings at the first presentation were analyzed. The LACNP was defined as over 70% area of capillary non-perfusion throughout the whole image retina. The mean follow-up duration was 12.4 ± 16.7 months. Follow-up data including extensive pan-retinal photocoagulation and surgical intervention and treatment outcomes were evaluated. RESULTS: A total of 43 eyes in 24 patients with LACNP were included, accounting for 3.3% of DR populations in the same period. The overall percentage of non-perfusion area was 79.1 ± 8.1%. All patients received proper control of diabetes and hypertension, and extensive pan-retinal laser photocoagulation. During the follow-up periods, 20 eyes (46.5%) developed severe neovascular complications, of which 15 eyes (34.9%) underwent vitrectomy and/or anti-glaucoma surgeries. Conservative therapies including glycemic control and supplemental laser photocoagulation were conducted in 23 eyes (53.5%) without neovascular complications. In the final follow-up, best corrected visual acuity improved or maintained stable in 19 eyes (44.2%) while deteriorated in 24 eyes (55.8%). CONCLUSIONS: The presence of LACNP is the hallmark of advanced DR and often indicates a poor visual outcome, although aggressive treatments may slow DR progression and maintain central vision for some time.

Physiological and proteomic analyses reveal the effects of exogenous nitrogen in diminishing Cd detoxification in Acacia auriculiformis.

Cadmium (Cd) has toxic effects on plants. Nitrogen (N), an essential element, is critical for plant growth, development and stress response. However, their combined effects on woody plants, especially in N-fixing tree species is still poorly understood. Our previous study revealed that the fast-growing Acacia auriculiformis showed strong Cd tolerance but the underlying mechanisms was not clear, which constrained its use in mine land reclamation. Herein, we investigated the physiological and proteomic changes in A. auriculiformis leaves to reveal the mechanisms of Cd tolerance and toxicity without N fertilizer (treatment Cd) and with excess N fertilizer (treatment CdN). Results showed that Cd tolerance in A. auriculiformis was closely associated with the coordinated gas exchange and antioxidant defense reactions under Cd treatment alone. Exogenous excessive N, however, inhibited plant growth, increased Cd concentrations, and weaken photosynthetic performance, thus, aggregated the toxicity under Cd stress. Furthermore, the aggregated Cd toxicity was attributed to the depression in the abundance of proteins, as well as their corresponding genes, involved in photosynthesis, energy metabolism (oxidative phosphorylation, carbon metabolism, etc.), defense and stress response (antioxidants, flavonoids, etc.), plant hormone signal transduction (MAPK, STN, etc.), and ABC transporters. Collectively, this study unveils a previously unknown physiological and proteomic network that explains N diminishes Cd detoxification in A. auriculiformis. It may be counterproductive to apply N fertilizer to fast-growing, N-fixing trees planted for phytoremediation of Cd-contaminated soils.

Synergistic Recognition-Triggered Charge Transfer Enables Rapid Visual Colorimetric Detection of Fentanyl.

As a new psychoactive substance, abuse of fentanyl (FTN) is currently spreading around the world, resulting in an urgent need of on-site and rapid analytical methods for detection of FTN. Here, we present a synergistic recognition strategy for rapid, cost-effective, selective, sensitive, and visual colorimetric detection of FTN by taking advantage of Rose Bengal (RB) as the specific probe. This assay is based on the halogen- and hydrogen-bonding interactions between them, generating a charge transfer and accompanying a red shift in the RB absorption band as well as color change from red to purple. The utility of the present visual colorimetric assay is demonstrated in aqueous solution, diluted urine, and domestic sewage samples. A detection limit of 0.7 mg·L-1 in aqueous solution is achieved, and the naked-eye detection of FTN is also realized in different real matrices within 6 min. Moreover, this method is insusceptible to interference from various substances (other opioids, cutting agents of street drugs, FTN precursors, amino acids, and small-molecular amines). Additionally, we successfully fabricate a smartphone-based portable device to determine FTN, which is appropriate for field tests. The present work not only provides the first visual assay for FTN but also reveals the molecular structure-property relationship, which will guide the design and development of various probes for recognizing FTN.

Genome-wide identification and analysis of DNA methyltransferase and demethylase gene families in Dendrobium officinale reveal their potential functions in polysaccharide accumulation.

BACKGROUND: DNA methylation is a conserved and important epigenetic modification involved in the regulation of numerous biological processes, including plant development, secondary metabolism, and response to stresses. However, no information is available regarding the identification of cytosine-5 DNA methyltransferase (C5-MTase) and DNA demethylase (dMTase) genes in the orchid Dendrobium officinale. RESULTS: In this study, we performed a genome-wide analysis of DoC5-MTase and DodMTase gene families in D. officinale. Integrated analysis of conserved motifs, gene structures and phylogenetic analysis showed that eight DoC5-MTases were divided into four subfamilies (DoCMT, DoDNMT, DoDRM, DoMET) while three DodMTases were divided into two subfamilies (DoDML3, DoROS1). Multiple cis-acting elements, especially stress-responsive and hormone-responsive ones, were found in the promoter region of DoC5-MTase and DodMTase genes. Furthermore, we investigated the expression profiles of DoC5-MTase and DodMTase in 10 different tissues, as well as their transcript abundance under abiotic stresses (cold and drought) and at the seedling stage, in protocorm-like bodies, shoots, and plantlets. Interestingly, most DoC5-MTases were downregulated whereas DodMTases were upregulated by cold stress. At the seedling stage, DoC5-MTase expression decreased as growth proceeded, but DodMTase expression increased. CONCLUSIONS: These results provide a basis for elucidating the role of DoC5-MTase and DodMTase in secondary metabolite production and responses to abiotic stresses in D. officinale.

Visual colorimetric detection of triacetone triperoxide based on a Fe(II)-promoted thermal decomposition process.

Triacetone triperoxide (TATP) explosives, a popular choice for terrorists, have been used in many violent terrorist attacks all over the world. However, simple, rapid, and on-site detection methods of TATP are still lacking. Herein, we present a visual colorimetric method for on-site and rapid detection of TATP based on a Fe(II)-promoted thermal decomposition process of TATP. We discovered that TATP can be decomposed into H2O2 under heating conditions, and it reacts with Fe2+ to produce hydroxyl radicals (˙OH) and Fe3+via the Fenton reaction. The resulting ˙OH and Fe3+ further oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) to a yellow oxidized product (oxTMB). These reaction processes remarkably promote the chemical equilibrium shift and decrease the activation energy. Using the TATP-Fe2+-TMB ternary chromogenic system, the present colorimetric assay for TATP shows a dynamic range of 0.5-30 µM with a low detection limit of 0.12 µM. Additionally, common substances (e.g., inorganic salts, small organic substances, and polymers) do not interfere with TATP detection. This assay can be used for analyzing TATP in real water and camouflage samples. Furthermore, a test-paper-based method was also successfully developed for visual, rapid and on-site detection of TATP.

Effects of elevated CO2 concentration and nitrogen addition on foliar phosphorus fractions of Mikania micranatha and Chromolaena odorata under low phosphorus availability.

Invasive plants rapidly spread in habitats with low soil phosphorus (P) availability and have triggered a sharp decline in the diversity of native species. However, no studies have explored how widespread invasive species acclimate to low soil P availability via changing foliar P fractions, especially under elevated atmospheric CO2 concentrations ([CO2 ]) and nitrogen (N) deposition. Here, an open-top chamber experiment was conducted to explore the effect of nutrient addition and elevated [CO2 ] on leaf traits and foliar functional P fractions (i.e., Pi, metabolite P, lipid P, nucleic acid P, and residual P) of two aggressive invasive species (Mikania micranatha and Chromolaena odorata). We found that foliar N/P ratios were more than 20, and P addition significantly increased plant biomass. Both results indicated P-limited plant growth at our studied site. Elevated [CO2 ], N and N + P addition greatly increased plant biomass, photosynthetic rates, and photosynthetic P-use efficiency (PPUE) in invasive species, but PPUE decreased with increasing P addition. Nitrogen addition slightly decreased the concentration of leaf total P, decreased foliar residual P, but increased metabolite P concentrations in invasive species. Similar changes in foliar P fractions were found under N + P addition. Phosphorus addition increased foliar P concentrations, which was strongly correlated with an increase in metabolite P concentrations in invasive species. Elevated [CO2 ] alleviated these effects and increased PPUE. The present results suggest that future elevated [CO2 ] and N deposition allow the invasive species to acclimate to low soil P availability and support their successful invasion by greatly reducing P allocation to non-metabolite foliar P fractions (i.e., nucleic acid P and residual P) to meet their demand of metabolite P for photosynthesis and exhibit a high PPUE.

Altering the substituents of salicylic acid to improve Berthelot reaction for ultrasensitive colorimetric detection of ammonium and atmospheric ammonia.

The Berthelot reaction is a classic method for detection of ammonium (NH4+) and atmospheric ammonia (NH3) by using salicylic acid (SA) as the chromogenic substrate. However, there lacks a method for improving the activity of the Berthelot reaction to enhance the analytical performance for detection of NH4+ and NH3. Here, five SA analogues with electron-withdrawing groups (-F) and electron-donating groups (-CH3 and -OCH3) at different positions of the aromatic ring have been chosen as the alternative to SA for Berthelot reaction. Among these analogues, 4-methoxysalicylic acid (4-OCH3-SA) shows the best colorimetric response and color change at a NH4+ concentration of 30 µM, and the sensitivity of 4-OCH3-SA-based colorimetric assay for NH4+ increases 1.75-fold compared with that of SA-based colorimetric method. This enhancement effect is attributed to the strong electron-donating property of 4-OCH3 group, activating the two-step electrophilic aromatic substitution reaction in the Berthelot reaction. Additionally, visual and sensitive detection of NH3 is realized, along with a low limit of detection down to 0.037 ppm. Furthermore, we demonstrate that this assay is reliable and practical for detection of NH4+ and NH3 in real water and air samples with good accuracy.

Association of UCP1 and UCP2 variants with diabetic retinopathy susceptibility in type-2 diabetes mellitus patients: a meta-analysis.

BACKGROUND: Genetic association of uncoupling proteins (UCPs) variants with the susceptibility of diabetic retinopathy (DR) in diabetes mellitus (DM) patients has been reported but with controversy. Here we aimed to conduct a meta-analysis to confirm the association of different UCPs variants with DR. METHODS: Three databases (Medline Ovid, Embase Ovid and CENTRAL) were applied in the literature search. Five genetic models, including allelic, homozygous, heterozygous, dominant and recessive models, were evaluated. Odds ratios (OR) were estimated under the random or fixed-effects models. Subgroup analyses, publication bias and sensitivity analyses were also conducted. RESULTS: Eleven studies on 2 UCPs variants (UCP1 rs1800592 and UCP2 rs659366) were included. Our meta-analysis showed that UCP1 rs1800592 was not associated with DR in type-2 DM patients, and UCP2 rs659366 also showed no association with DR. In the subgroup analyses on the stage of DR, allele G of UCP1 rs1800592 significantly increased the susceptibility of proliferative diabetic retinopathy (PDR) in type-2 DM patients in the allelic (OR = 1.26, P = 0.03) and homozygous models (OR = 1.60, P = 0.04). Subgroup analysis on ethnicity did not found any significant association of rs1800592 and rs659366 with DR. CONCLUSION: Our meta-analysis confirmed the association of UCP1 rs1800592 variant with PDR in patients with type-2 DM, suggesting its potential as a genetic marker for PDR prediction in population screening.

A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID-19. In the retrospective analysis, we report nine cases of COVID-19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.

COL2A1 protective variant reduces sporadic rhegmatogenous retinal detachment severity.

Rhegmatogenous retinal detachment (RRD) is the most common type of RD, the separation of neurosensory retina from the underlying retinal pigment epithelium. The RRD patients can be benefited from appropriate treatment if detected early, especially for the people predicted at high risk. In this study, we aimed to investigate the genetic association and clinical correlation of collagen type II alpha 1 (COL2A1) variants with sporadic RRD in a southern Chinese population. Totally 156 RRD patients and 254 control subjects were recruited, and 12 COL2A1 tag single nucleotide polymorphisms were genotyped by the TaqMan assay. The RRD patients had poorer visual acuity (P < 0.001) and lower intraocular pressure (IOP; P < 0.001) in their surgical eyes compared to the fellow eyes. The COL2A1 rs1793958 variant was significantly associated with RRD in the genotypic (P = 0.024), allelic (P = 0.011, odds ratio (OR) = 0.669), recessive (P = 0.011, OR = 0.384) and homozygous models (P = 0.007, OR = 0.348). RRD patients carrying the rs1793958 G allele had smaller retinal detachment area (P = 0.041) and smaller IOP differences (P = 0.046) between the surgical and fellow eyes compared to those carrying the wildtype AA genotype. In summary, this study revealed that the COL2A1 rs1793958 variant is associated with reduced risk of sporadic RRD, and patients carrying rs1793958 G allele have lower RRD severity.

Genome-Wide Identification and Expression Profile of TPS Gene Family in Dendrobium officinale and the Role of DoTPS10 in Linalool Biosynthesis.

Terpene synthase (TPS) is a critical enzyme responsible for the biosynthesis of terpenes, which possess diverse roles in plant growth and development. Although many terpenes have been reported in orchids, limited information is available regarding the genome-wide identification and characterization of the TPS family in the orchid, Dendrobium officinale. By integrating the D. officinale genome and transcriptional data, 34 TPS genes were found in D. officinale. These were divided into four subfamilies (TPS-a, TPS-b, TPS-c, and TPS-e/f). Distinct tempospatial expression profiles of DoTPS genes were observed in 10 organs of D. officinale. Most DoTPS genes were predominantly expressed in flowers, followed by roots and stems. Expression of the majority of DoTPS genes was enhanced following exposure to cold and osmotic stresses. Recombinant DoTPS10 protein, located in chloroplasts, uniquely converted geranyl diphosphate to linalool in vitro. The DoTPS10 gene, which resulted in linalool formation, was highly expressed during all flower developmental stages. Methyl jasmonate significantly up-regulated DoTPS10 expression and linalool accumulation. These results simultaneously provide valuable insight into understanding the roles of the TPS family and lay a basis for further studies on the regulation of terpenoid biosynthesis by DoTPS in D. officinale.