Optimized Machine Learning Model for Predicting Compressive Strength of Alkali-Activated Concrete Through Multi-Faceted Comparative Analysis.

Alkali-activated concrete (AAC), produced from industrial by-products like fly ash and slag, offers a promising alternative to traditional Portland cement concrete by significantly reducing carbon emissions. Yet, the inherent variability in AAC formulations presents a challenge for accurately predicting its compressive strength using conventional approaches. To address this, we leverage machine learning (ML) techniques, which enable more precise strength predictions based on a combination of material properties and cement mix design parameters. In this study, we curated an extensive dataset comprising 1756 unique AAC mixtures to support robust ML-based modeling. Four distinct input variable schemes were devised to identify the optimal predictor set, and a comparative analysis was performed to evaluate their effectiveness. After this, we investigated the performance of several popular ML algorithms, including random forest (RF), adaptive boosting (AdaBoost), gradient boosting regression trees (GBRTs), and extreme gradient boosting (XGBoost). Among these, the XGBoost model consistently outperformed its counterparts. To further enhance the predictive accuracy of the XGBoost model, we applied four state-of-the-art optimization techniques: the Gray Wolf Optimizer (GWO), Whale Optimization Algorithm (WOA), beetle antennae search (BAS), and Bayesian optimization (BO). The optimized XGBoost model delivered superior performance, achieving a remarkable coefficient of determination (R2) of 0.99 on the training set and 0.94 across the entire dataset. Finally, we employed SHapely Additive exPlanations (SHAP) to imbue the optimized model with interpretability, enabling deeper insights into the complex relationships governing AAC formulations. Through the lens of ML, we highlight the benefits of the multi-faceted synergistic approach for AAC strength prediction, which combines careful input parameter selection, optimal hyperparameter tuning, and enhanced model interpretability. This integrated strategy improves both the robustness and scalability of the model, offering a clear and reliable prediction of AAC performance.

Advancements in enzymatic reaction-mediated microbial transformation.

Enzymatic reaction-mediated microbial transformation has emerged as a promising technology with significant potential in various industries. These technologies offer the ability to produce enzymes on a large scale, optimize their functionality, and enable sustainable production processes. By utilizing microbial hosts and manipulating their genetic makeup, enzymes can be synthesized efficiently and tailored to meet specific industrial requirements. This leads to enhanced enzyme performance and selectivity, facilitating the development of novel processes and the production of valuable compounds. Moreover, microbial transformation and biosynthesis offer sustainable alternatives to traditional chemical methods, reducing environmental impact and promoting greener production practices. Microbial transformations enrich drug candidate diversity and enhance active ingredient potency, benefiting the pharmaceutical industry. Continued advancements in genetic engineering and bioprocess optimization drive further innovation and application development in Enzymatic reaction-mediated microbial transformation. The integration of AI for predicting enzymatic reactions and optimizing pathways marks a promising direction for future research. In summary, these technologies have the potential to revolutionize several industries by providing cost-effective, sustainable solutions.

Stimulation of an entorhinal-hippocampal extinction circuit facilitates fear extinction in a post-traumatic stress disorder model.

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging due to the fragile nature of fear extinction, for which ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed fear extinction. Gamma entrainment of vCA1 by deep brain stimulation (DBS) or noninvasive transcranial alternating current stimulation (tACS) of LEC persistently enhanced the PV-IN activity in vCA1, thereby promoting fear extinction. These results demonstrate that the LEC-vCA1 pathway forms a top-down motif to empower low gamma-band oscillations that facilitate fear extinction. Finally, application of low gamma DBS and tACS to a mouse model with persistent PTSD showed potent efficacy, suggesting that the dedicated LEC-vCA1 pathway can be stimulated for therapy to remove traumatic memory trace.

The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats.

Sunitinib, a novel anti-tumor small molecule targeting VEGFR, is prescribed for advanced RCC and GISTs. Sunitinib is primarily metabolized by the CYP3A enzyme. It is well-known that dexamethasone serves as a potent inducer of this enzyme system. Nonetheless, the effect of dexamethasone on sunitinib metabolism remains unclear. This study examined the effect of dexamethasone on the pharmacokinetics of sunitinib and its metabolite N-desethyl sunitinib in rats. The plasma levels of both compounds were measured using UHPLC-MS/MS. Pharmacokinetic parameters and metabolite ratio values were calculated. Compare to control group, the low-dose dexamethasone group and high-dose dexamethasone group decreased the AUC(0-t) values of sunitinib by 47 % and 45 %, respectively. Meanwhile, the AUC(0-t) values of N-desethyl sunitinib were increased by 2.2-fold and 2.4-fold in low-dose dexamethasone group and high-dose dexamethasone group, respectively. The CL values for sunitinib were both approximately 45 % higher in the two dexamethasone groups. Remarkably, metabolite ratio values increased over 5-fold in both low-dose dexamethasone group and high-dose dexamethasone group, indicating a significant enhancement of sunitinib metabolism by dexamethasone. Moreover, the total levels of sunitinib and its metabolite are also significantly increased. The impact of interactions on sunitinib metabolism, as observed with CYP3A inducers such as dexamethasone, is a crucial consideration for clinical practice. To optimize the dosage and prevent adverse drug events, therapeutic drug monitoring can be employed to avoid the toxicity from such interactions.

Construction of Cobalt-Containing Polyoxovanadate-Based Inorganic-Organic Hybrids as Heterogeneous Catalysts for the Selective Oxidation of Sulfides.

In order to develop efficient catalysts for the selective oxidation of sulfides, in this work, two polyoxovanadate-based inorganic-organic hybrids, [Co(H2O)3(3-bpfb)0.5(V2O6)]·(3-bpfb)0.5 (1) and [Co(H2O)2(4-bpfb)0.5(V2O6)] (2) [3-bpfb = N, N'-bis(3-pyridylformamide)-1, 4-benzenediamine, 4-bpfb = N, N'-bis(4-pyridylformamide)-1, 4-benzenediamine], were isolated under hydrothermal conditions. The structures of 1 and 2 embodied two kinds of different cobalt-containing polyoxovanadate-based inorganic chains. Compound 1 contained a one-dimensional inorganic zigzag chain created by the aggregation of {V2O6} clusters with each other, on which Co (II) ions were fixed. But it was an inorganic dimeric chain constructed from two linear {V2O6} cluster-based chains gathered by Co (II) ions in 2. The 3-bpfb and 4-bpfb ligands, as the bidentate linkers, coordinated with two Co (II) ions from adjacent chains to organize them into two-dimensional layers. The hydrogen bonds made important contributions to the formation of supramolecular structures of the two compounds. The two compounds served as heterogeneous catalysts and exhibited efficient activity for the selective oxidation of sulfide to sulfoxide and could be reused at least six times without loss of catalytic activity and stability.

Natural Affinity Driven Modification by Silicene to Construct a "Thermal Switch" for Tumorous Bone Loss.

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.

Up-regulating GABA transporter-3 in the zona incerta prevents surgery-induced memory impairment in mice.

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.

Comparison of three-dimensional heads-up system versus traditional microscopic system in medical education for vitreoretinal surgeries: a prospective study.

BACKGROUND: To compare the value and efficiency of the three-dimensional (3D) heads-up surgical system and traditional microscopic (TM) system in teaching and learning vitreoretinal surgeries. METHODS: Twenty ophthalmologists and scrub nurses were recruited as teachers, and 45 junior ophthalmology residents and trainee doctors, trainee nurses, and medical students were recruited as observers. Each teacher and observer were assigned to both a 3D-assisted and TM-assisted vitreoretinal surgery and then asked to complete satisfaction questionnaires for both surgical systems at the end of each surgery. RESULTS: The 3D heads-up surgical system was rated significantly higher in most of the subscales and overall satisfaction score by both teachers and observers (P < 0.05). However, ratings for instrument adjustment were significantly higher in the TM group compared to the 3D group for junior ophthalmology residents and trainee doctors (6.1 ± 1.7 vs. 8.8 ± 1.1, P < 0.001). CONCLUSIONS: The 3D heads-up surgical system has great didactical value in the medical education of vitreoretinal surgeries, but it is important to consider the specific needs of different learners when choosing between the two systems. TRIAL REGISTRATION: Not applicable.

Central and Peripheral Changes in Retinal Vein Occlusion and Fellow Eyes in Ultra-Widefield Optical Coherence Tomography Angiography.

Purpose: To explore the central and peripheral retinal and choroidal changes in retinal vein occlusion (RVO) and fellow eyes using ultra-widefield swept-source optical coherence tomography angiography (UWF-SS-OCTA). Methods: Fifteen ischemic central RVO (CRVO), 15 branch RVO (BRVO), and 15 age-matched healthy controls were prospectively recruited. Retinal and choroidal parameters, including retinal vessel flow density (VFD) and vessel linear density (VLD), choroidal vascularity volume (CVV), choroidal vascularity index (CVI), and VFD in the large and medium choroidal vessels (LMCV-VFD), were measured in the central and peripheral regions of the 24 × 20-mm UWF-SS-OCTA images. Results: Ischemic CRVO and BRVO eyes showed increased foveal avascular zone area, perimeter, and acircularity index (AI) compared to their fellow eyes and healthy control eyes, and RVO fellow eyes also had larger AI values than controls (P < 0.05). For ischemic CRVO and BRVO eyes versus control eyes, VFD, VLD, CVV, CVI, and LMCV-VFD decreased, but retinal thickness and volume in the superficial capillary plexus, deep capillary plexus, and whole retina increased (P < 0.05). Moreover, RVO fellow eyes also showed significantly decreased retinal VFD, LMCV-VFD, and CVI, as well as increased retinal thickness and volume, compared with control eyes (P < 0.05). Alterations were not consistent throughout the retina, as they involved only the peripheral or central regions in some cases. Conclusions: The affected and unaffected fellow eyes of RVO patients both demonstrated central and/or peripheral structural and vascular alterations in the retina and choroid. Because UWF-SS-OCTA enables visualization and evaluation of the vasculature outside the posterior pole, it presents a promising approach to more fully characterize vascular alterations in RVO.

Impacts of angiotensin II on retinal artery changes in apolipoprotein E deficient mice.

AIM: To investigate the impacts of angiotensin II (Ang II) on retinal artery changes in apolipoprotein E deficient (apoE-/-) mice. METHODS: apoE-/- male mice were infused by minipumps with Ang II at 1000 ng/kg·min (Ang II group) or saline (control group) for 28d. They were underwent ophthalmic fundus examination on day 0, 14, and 28 of infusion. Histopathologic examination, ribonucleic acid (RNA) sequencing and local Ang II measurement of retinas were conducted. RESULTS: Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28. Optical coherence tomography revealed the ganglion cell and inner plexiform layer (GCIPL) thickness in the control group was significantly thinner than that in Ang II group (P<0.001). Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group. Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions, including increased swelling, roughness, disorganization of the retinal vasculature, and vacuoles formation. RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II. The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group (P=0.086). CONCLUSION: Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE-/- mice, causing aggravation of atherosclerotic lesions, more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.

Glutamatergic Projection from the Ventral Tegmental Area to the Zona Incerta Regulates Fear Response.

Innate defensive behavior is important for animal survival. The Vglut2+ neurons in the ventral tegmental area (VTA) have been demonstrated to play important roles in innate defensive behaviors, but the neural circuit mechanism is still unclear. Here, we find that VTA - zona incerta (ZI) glutamatergic projection is involved in regulating innate fear responses. Combining calcium signal recording and chemogentics, we find that VTA-Vglut2+ neurons respond to foot shock stimulus. Inhibition of VTA-Vglut2+ neurons reduces foot shock-evoked freezing, while chemogentic activation of these neurons results in an enhanced fear response. Using viral tracing and immunofluorescence, we show that VTA - Vglut2+ neurons send direct excitatory outputs to the ZI. Moreover, we find that the activity of VTAVglut2 - ZI projection is pivotal in modulating fear response. Together, our study reveals a new VTA - ZI glutamatergic circuit in mediating innate fear response and provides a potential target for treating post-traumatic stress disorder.

Abrogation of ATR function preferentially augments cisplatin-induced cytotoxicity in PTEN-deficient breast cancer cells.

Targeting replication stress response is currently emerging as new therapeutic strategy for cancer treatment, based on monotherapy and combination approaches. As a key sensor in response to DNA damage, ataxia telangiectasia and rad3-related (ATR) kinase has become a potential therapeutic target as tumor cells are to rely heavily on ATR for survival. The tumor suppressor phosphatase and tensin homolog (PTEN) plays a crucial role in maintaining chromosome integrity. Although ATR inhibition was recently confirmed to show a synergistic inhibitory effect in PTEN-deficient triple-negative breast cancer cells, the molecular mechanism needs to be further elucidated. Additionally, whether the PTEN-deficient breast cancer cells are more preferentially sensitized than PTEN-wild type breast cancer cells to cisplatin plus ATR inhibitor remains unanswered. We demonstrate PTEN dysfunction promotes the killing effect of ATR blockade through the use of RNA interference for PTEN and a highly selective ATR inhibitor VE-821, and certify that VE-821 (1.0 µmol/L) aggravates cytotoxicity of cisplatin on breast cancer cells, especially PTEN-null MDA-MB-468 cells which show more chemoresistance than PTEN-expressing MDA-MB-231 cells. The co-treatment with VE-821 and cisplatin significantly reduced cell viability and proliferative capacity compared with cisplatin mono-treatment (P < 0.05). The increased cytotoxic activity is tied to the enhanced poly (ADP-ribose) polymerase (PARP) cleavage and consequently cell death due to the decrease in phosphorylation levels of checkpoint kinases 1 and 2 (CHK1/2), the reduction of radiation sensitive 51 (RAD51) foci and the increase in phosphorylation of the histone variant H2AX (γ-H2AX) foci (P < 0.05) as well. Together, these findings suggest combination therapy of ATR inhibitor and cisplatin may offer a potential therapeutic strategy for breast tumors.

[Quality of moxa with different leaf-to-moxa ratios based on correlation analysis of thermogravimetric properties, cellulose content, and microscopic characteristics of non-secretory trichomes].

The quality of moxa is a key factor affecting the efficacy of moxibustion. Traditional moxa grades are evaluated by the leaf-to-moxa ratio, but there is a lack of support from scientific data. Scanning electron microscopy(SEM), Image Pro Plus, Van Soest method, and stimultaneous thermal analysis(TGA/DSC) were used to characterize the scientific implication of the combustion differences between moxa with different leaf-to-moxa ratios(processed by crusher). The results showed that the median lengths from non-secretory trichomes(NSTs) of natural NSTs and moxa with leaf-to-moxa ratios of 3∶1, 5∶1, 10∶1, and 15∶1 were 542.46, 303.24, 291.18, 220.69, and 170.61 µm, respectively. The cellulose content of moxa increased significantly(P<0.05) with the increase in leaf-to-moxa ratio and the combustion parameters(T_i, t_i, D_i, C,-R_p,-R_v, S, D_b, and J_(total)) all showed an increasing trend. The correlation results showed that the burning properties of moxa(T_i,-R_v, t_i, and J_2) were significantly and positively correlated with cellulose content. NSTs with a length of 1-200 µm were significantly and positively correlated with J_2. NSTs with a length of 200-600 µm were significantly and positively correlated with J_1, T_(peak2), T_(peak1), and-R_v, and negatively correlated with J_(total), T_b, and t_b. As the leaf-to-moxa ratio increases, the NSTs in the moxa become shorter and the cellulose content increases, which is more conducive to ignition performance, heat release, and a milder, longer-lasting burn. The "NSTs-cellulose-TGA/DSC" quantitative evaluation method scientifically reveals the scientific connotation of the combustion of moxa with different leaf-to-moxa ratios and provides a scientific basis for the establishment of quality evaluation methods for moxa with different leaf-to-moxa ratios.

The incidence, risk factors, management and prognosis of postoperative systemic complications after ophthalmic surgery: a retrospective study at a tertiary, academic referral hospital over a decade.

PURPOSE: To explore the incidence, risk factors, management and prognosis of systemic complications after ophthalmic surgeries. METHODS: A retrospective review of hospitalized patients undergoing ophthalmic surgeries between 2012 and 2022 at Peking Union Medical College Hospital was performed to summarize and analyse the postoperative systemic complications. Multivariate logistic and linear regression analyses were conducted to clarify the risk factors of postoperative systemic complications and factors associated with the severity of adverse events. RESULTS: A total of 34,841 patients underwent inpatient ophthalmic surgery, among which 162 systemic complications occurred in 150 patients during postoperative hospitalization. The overall incidence rate was 0.4%, with cardiovascular events (48.1%), digestive events (13.6%) and fever (12.3%) being the leading causes. About 17.3% of the cases had conditions improved after observation, 19.1% after symptomatic treatment, 54.9% had consultation with specific intervention and 8.6% were transferred to the corresponding departments for specialized treatment. For the prognosis, 93.8% had condition improved, 5.6% chose voluntary discharge without improvement, and one patient died of respiratory failure caused by postoperative pulmonary infection. The worse ADL (activities of daily living) grading, indication of primary intraocular lymphoma or intraocular tumour, surgery of simple pars plana vitrectomy (PPV), PPV with silicone oil tamponade, PPV with gas tamponade, general anaesthesia, history of diabetes mellitus (DM), chronic heart failure and digestive system disease were the risk factors positively correlated with postoperative systemic complications (p < .05). The worse ADL grading, history of DM and respiratory system disease were also positively correlated with the severity of the adverse events (p < .05). CONCLUSIONS: The incidence of postoperative systemic complications was low among patients undergoing ophthalmic surgery, most were mild and could be relieved after observation, symptomatic or specialist consultation. Patients with worse ADL and history of DM should be paid extra attention.

[Source Analysis and Health Risk Assessment of Heavy Metals in the Groundwater of Shijiazhuang, a Typical City in North China Plain].

Increasing attention has been paid to the heavy metal pollution in groundwater. The source analysis and risk assessment of heavy metals will provide data and method support for the targeted control of heavy metal pollution in groundwater. In this study, 20 sampling sites were selected in Shijiazhuang City. The APCS-MLR model and health risk model were applied to analyze and evaluate the pollution sources and health risks of 10 types of heavy metals in the groundwater of Shijiazhuang. The results showed that ① the mean concentration of heavy metals in groundwater followed the order of Fe>Zn>Mn>Cu>Al>Pb>Cr>As>Cd>Hg, and the mean ρ(Fe) and ρ(Pb) were 260.3 µg·L-1 and 10.01 µg·L-1, respectively. According to the results of the single factor and Nemerow index, Pb, Fe, and Cd primarily contributed to the heavy metal pollution in the groundwater. ② The concentration of heavy metals ranged from 47.30 to 2560 µg·L-1. In terms of spatial distribution, the highest concentration appeared at S3 (2560 µg·L-1), whereas the lowest concentration was at S9 (47.30 µg·L-1). ③ Source analysis results showed that industrial and agricultural activities, transportation emission, and geological background were the major heavy metal sources, among which the contribution of industrial and agricultural activities was the highest (47.83%). ④ The industrial-agricultural activities posed a potential threat to adults (HI>1); however, the non-cancer and the cancer risks of other sources for both adults and children were at an acceptable level (HI<1) and potential threat level, respectively; industrial-agricultural activities were the major source of non-cancer (adults:52.46%, children:52.45%) and cancer risks (adults:65.22%, children:65.69%), among which Cd and As showed high cancer risk. Therefore, to ensure the safety of the groundwater environment, strictly controlling the pollution sources and further strengthening the risk control of heavy metal pollution in groundwater are necessary.

[Source Apportionment and Source-specific Risk of Typical Antibiotics in Baiyangdian Lake].

The current situation of antibiotic pollution in lakes is critical. At present, most of the previous studies on antibiotics in lakes have focused on the spatiotemporal distribution and risk assessment, while less attention has been paid to the source apportionment. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of tetracyclines (TCs), sulfonamides (SAs), and quinolones (QNs) in the samples. The source apportionment and source-specific risk of typical antibiotics in the study area were analyzed using the combination of a PMF model and risk quotients (RQ). The results showed that ① the total concentrations of target antibiotics (Σ antibiotics) ranged from ND to 2635 ng·L-1 for surface water and from ND to 259.8 ng·g-1 for sediments. ② The spatial distribution of QNs in surface water decreased from west to east, SAs decreased from middle to north and south, and TCs increased from middle to north and south. In the sediment, QNs decreased from middle to east and west, whereas SAs and TCs increased from east to west. ③ Aquaculture was the major antibiotic source, accounting for the highest proportion (33.2%), followed by sewage treatment plants (29.2%), livestock activities (18.9%), and domestic sewage (18.7%). ④ The ecological risk assessment results showed that enrofloxacin and flumequine were at a medium-high risk level. ⑤ For the spatial distribution of source-specific risk, the results showed that the aquaculture at S1 was at a high risk level, whereas the source-specific risks for other sites were at a medium-low risk level. In terms of source types, aquaculture was at a medium-high risk level, whereas the other sources were at a medium-low risk level. Therefore, considering the major sources and source-specific risk level of antibiotics, more precise and scientific antibiotic risk control should be adopted in Baiyangdian Lake.

[Spatial-temporal Changes and Driving Factors of Soil Microbial Communities in a Typical City of North China Plain].

The structure and function of microbial communities are affected by several environmental factors. To clarify the spatial-temporal changes and main influencing factors of soil microbial communities in a typical pharmaceutical city, it is urgent to study the spatial-temporal changes in microbial communities in soils for typical cities. Shijiazhuang City was selected as the study area, and 12 sampling sites were selected. The topsoil was collected in June (summer) and September (autumn) of 2021. The 16S rRNA high-throughput sequencing technology was used to study the structure and function of microbial communities in the soil and explore their spatial-temporal changes. Concurrently, Pearson correlation analysis was applied to establish the correlation between the microbial community and environmental factors, and identify the main driving factors of temporal and spatial changes in the microbial community. The results showed that:① Actinobaciota and Proteobateria were the main dominant bacteria in the surface soil of Shijiazhuang City; at the phylum level, the relative abundance of Actinobacteria and Proteobateria decreased from summer to autumn; at the genus level, the dominant genera were Arthrobacter and unknown genera in summer and Arthrobacter and Candidatus_Nitrocosmicus in autumn, which showed significant seasonal differences (P<0.05). ② For seasonal variation, the mean values of the Simpson, Ace, and Chao indices increased, whereas the mean values of OTU decreased; for spatial variation, the Shannon and Simpson indices showed significant spatial difference (P<0.01 and P<0.05). ③ There were no significant spatial-temporal differences in various functional genes; thereinto, the relative abundances of energy production and transformation functional genes were the highest (24.06%-24.84% in summer and 24.63%-25.98% in autumn, respectively). ④ The compositions of microbial community, diversity index, and functional genes were significantly correlated with quinolone antibiotics (QNs), total phosphorus (TP), and nitrate nitrogen (NO3--N), most significantly correlated with QNs (|r|>0.900), which indicated that antibiotics were the main driving factor of soil microbial communities. Therefore, to ensure the stability of microbial community structure and function in urban soil, the comprehensive management and control of antibiotic pollution in soil should be further strengthened.

SGLT2 inhibitors alleviated podocyte damage in lupus nephritis by decreasing inflammation and enhancing autophagy.

OBJECTIVES: The protective role of sodium glucose cotransporter 2 (SGLT2) inhibitors in renal outcomes has been revealed by large cardiovascular outcome trials among patients with type 2 diabetes. However, the effect of SGLT2 inhibitors on lupus nephritis (LN) and its underlying mechanisms remain unknown. METHODS: We applied empagliflozin treatment to lupus-prone MRL/lpr mice to explore the renal protective potential of SGLT2 inhibitors. An SGLT2 knockout monoclonal podocyte cell line was generated using the CRISPR/Cas9 system to examine the cellular and molecular mechanisms. RESULTS: In MRL/lpr mice treated with empagliflozin, the levels of mouse anti-dsDNA IgG-specific antibodies, serum creatinine and proteinuria were markedly decreased. For renal pathology assessment, both the glomerular and tubulointerstitial damages were lessened by administration of empagliflozin. The levels of SGLT2 expression were increased and colocalised with decreased synaptopodin in the renal biopsy samples from patients with LN and MRL/lpr mice with nephritis. The SGLT2 inhibitor empagliflozin could alleviated podocyte injury by attenuating inflammation and enhanced autophagy by reducing mTORC1 activity. Nine patients with LN treated with SGLT2 inhibitors with more than 2 months of follow-up showed that the use of SGLT2 inhibitors was associated with a significant decrease in proteinuria from 29.6% to 96.3%. Moreover, the estimated glomerular filtration rate (eGFR) was relatively stable during the treatment with SGLT2 inhibitors. CONCLUSION: This study confirmed the renoprotective effect of SGLT2 inhibitors in lupus mice, providing more evidence for non-immunosuppressive therapies to improve renal function in classic autoimmune kidney diseases such as LN.

Clinical features of Cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome and efficacy of the current therapy.

Background: Cytomegalovirus retinitis (CMVR) is the most common and sight-threatening opportunistic retinal infection in patients with acquired immunodeficiency syndrome (AIDS) and several controversies remain to be settled. We aimed to summarize the current evidence and clarify the clinical features and prognosis of CMVR in AIDS patients. Methods: The databases PubMed, EMBASE, and Ovid from inception to April 2022 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval (CI) were calculated using the Freeman-Tukey variant of arcsine square transformation. Results: We finally included 236 studies comprising 20,214 patients. CMVR in AIDS was male-dominated (88%, 95%CI 86%-89%), with 57% (95%CI 55%-60%) aged <41 years and 44% (95%CI 41%-47%) being bilaterally involved. CMVR was preponderant in AIDS patients with the following characteristics: white and non-Hispanic, homosexual, HIV RNA load ≥ 400 copies/mL, and CD4+ T-cells <50 cells/µL. The positivity of CMV-DNA in blood, aqueous humor, and vitreous humor was 66% (95%CI 52%-79%), 87% (95%CI 76%-96%), and 95% (95%CI 85%-100%), respectively. The most common symptoms were blurred vision (55%, 95%CI 46%-65%), followed by asymptomatic, visual field defect, and floaters. CMVR was first diagnosed and regarded as the clue to AIDS diagnosis in 9% (95%CI 6%-13%) of CMVR patients. Approximately 85% (95%CI 76%-93%) of the CMVR patients have received cART. CMVR remission was observed in 72%-92% of patients depending on the specific category of anti-CMV therapy. The general incidence of CMVR-related RD in the entire course was 24% (95%CI 18%-29%), of which most patients received PPV with SO or gas tamponade and the rate of anatomic success was 89% (95%CI 85%-93%). Conclusion: CMVR is a common opportunistic infection with diverse clinical features in AIDS patients, preponderant in those who are male, homosexual, or with CD4+ T-cells <50 cells/µL. Current therapies for CMVR and CMVR-related RD were shown to be effective. Early detection and routine ophthalmic screening should be promoted in AIDS patients. Systematic review registration: PROSPERO, identifier CRD42022363105.

Endogenous Endophthalmitis at a Tertiary Referral Center in China: A Retrospective Study Over Three Decades.

PURPOSE: To investigate the etiology, pathogens, treatment, and prognosis of endogenous endophthalmitis (EE). METHODS: Patients diagnosed with EE over three decades at Peking Union Medical College Hospital were retrospectively reviewed and analyzed. RESULTS: A total of 97 eyes from 81 patients were included. Diabetes was the most common predisposing medical condition (34.6%). Klebsiella pneumoniae (31.3%) and Candida albicans (32.8%) were the most common pathogens. Liver abscess (20.6%) was the predominant cause EE due to liver abscess had a worse initial visual acuity (P < 0.05). Patients who initially underwent pars plana vitrectomy (PPV)+silicone oil tamponade underwent fewer total treatments (P < 0.05). In the past 10 years, the proportion of Gram-positive cocci, Gram-negative bacilli, and Candida showed an upward trend. Over the past 15 years, EE after liver abscess and immunosuppression has increased, while EE from genitourinary systems has decreased. CONCLUSION: EE was a devastating intraocular disease with a poor visual prognosis. The initial condition and prognosis of EE after liver abscess were the worst. PPV+silicone oil tamponade as an initial treatment may reduce additional therapy.