Assessing muscle invasion in bladder cancer via virtual biopsy: a study on quantitative parameters and classical radiomics features from dual-energy CT imaging.

OBJECTIVE: To evaluate the prediction value of Dual-energy CT (DECT)-based quantitative parameters and radiomics model in preoperatively predicting muscle invasion in bladder cancer (BCa). MATERIALS AND METHODS: A retrospective study was performed on 126 patients with BCa who underwent DECT urography (DECTU) in our hospital. Patients were randomly divided into training and test cohorts with a ratio of 7:3. Quantitative parameters derived from DECTU were identified through univariate and multivariate logistic regression analysis to construct a DECT model. Radiomics features were extracted from the 40, 70, 100 keV and iodine-based material-decomposition (IMD) images in the venous phase to construct radiomics models from individual and combined images using a support vector machine classifier, and the optimal performing model was chosen as the final radiomics model. Subsequently, a fusion model combining the DECT parameters and the radiomics model was established. The diagnostic performances of all three models were evaluated through receiver operating characteristic (ROC) curves and the clinical usefulness was estimated using decision curve analysis (DCA). RESULTS: The normalized iodine concentration (NIC) in DECT was an independent factor in diagnosing muscle invasion of BCa. The optimal multi-image radiomics model had predictive performance with an area-under-the-curve (AUC) of 0.867 in the test cohort, better than the AUC = 0.704 with NIC. The fusion model showed an increased level of performance, although the difference in AUC (0.893) was not statistically significant. Additionally, it demonstrated superior performance in DCA. For lesions smaller than 3 cm, the fusion model showed a high predictive capability, achieving an AUC value of 0.911. There was a slight improvement in model performance, although the difference was not statistically significant. This improvement was observed when comparing the AUC values of the DECT and radiomics models, which were 0.726 and 0.884, respectively. CONCLUSION: The proposed fusion model combing NIC and the optimal multi-image radiomics model in DECT showed good diagnostic capability in predicting muscle invasiveness of BCa.

Reproductive and germ-cell mutagenic effects of poly-and perfluoroalkyl substances (PFAS) to Caenorhabditis elegans after multigenerational exposure.

Per- and polyfluoroalkyl substances (PFAS) are a class of globally ubiquitous persistent organic pollutants (POPs). The developmental and reproductive toxicity of PFAS have attracted considerable attention. However, the influence of PFAS exposure on genomic stability of germ cells remains unexplored. In this study, we evaluated long-term reproductive toxicity of environmentally relevant levels of four long-chain PFAS compounds: perfluorooctanoic acid (PFOA, C8), perfluorononanoic acid (PFNA, C9), perfluorodecanoic acid (PFDA, C10), and perfluorooctanesulfonic acid (PFOS, C8), and examined their germ-cell mutagenicity in Caenorhabditis elegans. Our findings reveal that multigenerational exposure to PFAS exhibited minor impacts on development and reproduction of worms. Among all tested PFAS, PFNA significantly increased mutation frequencies of progeny by preferentially inducing T:A â†’ C:G substitutions and small indels within repetitive regions. Further analysis of mutation spectra uncovered elevated frequencies of microhomology-mediated deletions and large deletions in PFOA-treated worms, indicating its potential activity in eliciting DNA double-strand breaks. This study provides the first comparative analysis of the genome-wide mutational profile of PFAS compounds, underscoring the importance of assessing germ-cell mutagenic actions of long-chain PFAS.

Unraveling the synergistic mechanisms of coagulation combined with oxidation for the treatment of sewer overflow: The interaction between iron species and NaClO.

During wet weather, sewer overflow pollution can pose a serious threat to surface water. In order to reduce the impact of overflow discharge on receiving waters, ferric chloride (Fe(Ⅲ))/potassium ferrate (Fe(Ⅵ))/polyacrylamide (PAM) coagulation (Fe(Ⅲ)/Fe(Ⅵ)/PAM) combined with sodium hypochlorite (NaClO) oxidation was proposed. Different combinations were constructed, including pre-oxidation coagulation (NaClO-Fe(Ⅲ)/Fe(Ⅵ)/PAM), pre-coagulation oxidation (Fe(Ⅲ)/Fe(Ⅵ)/PAM-NaClO), and synchronous coagulation oxidation (NaClO+Fe(Ⅲ)/Fe(Ⅵ)/PAM). The combined processes achieved efficient removal of conventional contaminants, and the produced byproducts were controlled, especially in the NaClO-Fe(Ⅲ)/Fe(Ⅵ)/PAM. The obvious discrepancy in the sulfamethoxazole (SMX) removal was observed in different processes. NaClO affected the distribution of hydrolyzed iron species, and the proportion of active iron in the NaClO-Fe(Ⅲ)/Fe(Ⅵ)/PAM significantly increased. More complexation sites were generated in the NaClO-Fe(Ⅲ)/Fe(Ⅵ)/PAM, which can complex with the coagulant and then effectively transfer to the flocs. The composition of the flocs further confirmed the differences in coagulation characteristics. The generated·OH played a crucial role in SMX removal in the NaClO+Fe(Ⅲ)/Fe(Ⅵ)/PAM, and ClO·was responsible for partial removal of ammonia nitrogen (NH4+-N). The contribution of high-valent iron species was confirmed, and the introduction of NaClO promoted the generation of iron species. This study may provide an ideal for overflow treatment to improve the urban water environment.

Chitinase-assisted winner: nematodes antagonize symbiotic microbes.

Nematodes do not merely siphon off plant resources but also sabotage the plant's mutualistic relationships with beneficial microbes. Yang and colleagues elegantly elucidated this generalizable molecular antagonism, revealing how Heterodera glycines, the notorious soybean cyst nematode (SCN), suppresses beneficial microbial symbiosis through a specific chitinase, HgCht2.

Achieving sub-millisievert CT colonography for accurate colorectal tumor detection using smart examination protocols: a prospective self-controlled study.

PURPOSE: To assess the feasibility of combining Auto-kVp selection technique, higher preset ASIR-V and noise index (NI) to realize individualized sub-mSv CT colonography (CTC) for accurate colorectal tumor detection and localization. METHODS: Ninety patients with suspected colorectal cancer (CRC) were prospectively enrolled to undergo standard dose CTC (SDCTC) in the prone and ultra-low dose CTC (ULDCTC) in the supine position. SDCTC used 120 kVp, preset ASIR-V of 30%, SmartmA for a NI of 13; ULDCTC used Auto-kVp selection technique with 80 or 100 kVp, preset ASIR-V of 60%, SmartmA for a NI of 13 for 80 kVp, and NI of 15 for 100 kVp. The effective dose (ED), image quality [signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of colorectal neoplasms] between the two protocols were compared and the accuracies of tumor locations were evaluated for CTC in comparison with the surgery results. RESULTS: The mean ED of the ULDCTC-80 kVp subgroup was 0.70 mSv, 71.43% lower than the 2.45 mSv for the 120 kVp group, while that of the ULDCTC-100 kVp subgroup was 0.98 mSv, 73.00% lower than the 3.63 mSv for the 120 kVp group (P < 0.001). The tumor SNR and CNR of the ULDCTC were higher than those of SDCTC (P < 0.05), while there was no difference in the subjective image quality between them with good inter-observer agreement (Kappa: 0.805-0.923). Both SDCTC and ULDCTC groups had high detection rate of colorectal tumors, along with good consistency in determining tumor location compared with surgery reports (Kappa: 0.718-0.989). CONCLUSION: The combination of Auto-kVp selection, higher preset ASIR-V and NI achieves individualized sub-mSv CTC with good performance in detecting and locating CRC with surgery and consistent results between SDCTC and ULDCTC.

Loss of ON-Pathway Function in Mice Lacking Lrit3 Decreases Recovery From Lens-Induced Myopia.

Purpose: To determine whether the Lrit3-/- mouse model of complete congenital stationary night blindness with an ON-pathway defect harbors myopic features and whether the genetic defect influences the recovery from lens-induced myopia. Methods: Retinal levels of dopamine (DA) and 3,4 dihydroxyphenylacetic acid (DOPAC) from adult isolated Lrit3-/- retinas were quantified using ultra performance liquid chromatography after light adaptation. Natural refractive development of Lrit3-/- mice was measured from three weeks to nine weeks of age using an infrared photorefractometer. Susceptibility to myopia induction was assessed using a lens-induced myopia protocol with -25 D lenses placed in front of the right eye of the animals for three weeks; the mean interocular shift was measured with an infrared photorefractometer after two and three weeks of goggling and after one and two weeks after removal of goggles. Results: Compared to wild-type littermates (Lrit3+/+), both DA and DOPAC were drastically reduced in Lrit3-/- retinas. Natural refractive development was normal but Lrit3-/- mice showed a higher myopic shift and a lower ability to recover from induced myopia. Conclusions: Our data consolidate the link between ON pathway defect altered dopaminergic signaling and myopia. We document for the first time the role of ON pathway on the recovery from myopia induction.

GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.

During Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) communicates with GLI transcription factors by binding the protein kinase A catalytic subunit (PKA-C) and physically blocking its enzymatic activity. Here, we show that GPCR kinase 2 (GRK2) orchestrates this process during endogenous mouse and zebrafish Hh pathway activation in the primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction. Reconstitution studies reveal that GRK2 phosphorylation enables active SMO to bind PKA-C directly. Lastly, the SMO-GRK2-PKA pathway underlies Hh signal transduction in a range of cellular and in vivo models. Thus, GRK2 phosphorylation of ciliary SMO and the ensuing PKA-C binding and inactivation are critical initiating events for the intracellular steps in Hh signaling. More broadly, our study suggests an expanded role for GRKs in enabling direct GPCR interactions with diverse intracellular effectors.

Optimizing the placement of medical wastewater outlets in sewer systems to reduce chemical consumption at wastewater treatment plants.

The severely low influent chemical oxygen demand (COD) concentration at wastewater treatment plants (WWTPs) has become a critical issue. A key factor is the excessive biodegradation of organic matter by microbial communities within sewer systems. Intense disinfection commonly adopted for medical wastewater leads to abundant residual chlorine entering sewers, likely causing significant changes in microbial communities and sewage quality in sewers, yet our understanding is limited. Through long-term sewer simulation batch tests, this study revealed the response mechanism of microbial communities to residual chlorine and its impact on organic matter concentration in sewage. Under residual chlorine stress, microbial community structure rapidly changed, and more complex microbial interactions were observed. Besides, pathways related to stress response such as two-component system were significantly enriched; pathways related to energy metabolism (such as carbon fixation in prokaryotes and citrate cycle) in microbial communities were inhibited, and carbon metabolism shifted from the Embden-Meyerhof pathway to the pentose phosphate pathway to enhance cellular reducing power, reduce oxidative stress, and consequently decrease organic matter degradation. Therefore, compared to sewers with normal disinfection, concentrations of COD and dissolved organic carbon in sewage under chlorine stress increased by 12.6 % and 7.4 %, respectively. Besides, the decay and transformation of residual chlorine in sewers were explored. These findings suggest a new approach to medical wastewater discharge management: placing the medical wastewater outlet at the upstream in sewer systems, which ensures that residual chlorine consumption reaches maximum during long-distance transportation, mitigating its harmful effects on WWTPs, and increases the influent organic matter concentration, thereby reducing the need for additional carbon sources.

Discovery of Novel Mcl-1 Inhibitors with a 3-Substituted-1H-indole-1-yl Moiety Binding to the P1-P3 Pockets to Induce Apoptosis in Acute Myeloid Leukemia Cells.

Mcl-1 is a main antiapoptotic protein in acute myeloid leukemia (AML) and is used as a target to develop inhibitors. Currently, potent Mcl-1 inhibitors primarily interact with the P2-P4 pockets of Mcl-1, but pharmacological modulation by targeting the P1 pocket is less explored. We designed a series of 1H-indole-2-carboxylic acid compounds as novel Mcl-1 inhibitors occupying the P1-P3 pockets and evaluated their Mcl-1 inhibition and apoptosis induction in AML cells. Two-dimensional 15N-HSQC spectroscopy indicated that 47 (Ki = 24 nM) bound to the BH3 binding groove, occupied the P1 pocket in Mcl-1, and formed interactions with Lys234 and Val249. 47 exhibited good microsomal stability and pharmacokinetic profiles, with low potential risk of cardiotoxicity. 47 inhibited tumor growth in HL-60 and THP-1 xenograft models with growth inhibition rate of 63.7% and 57.4%, respectively. Collectively, 47 represents a novel Mcl-1 inhibitor targeting the P1-P3 pockets with excellent antileukemia effects.

Air pollution associated with cardiopulmonary disease and mortality among participants with preserved ratio impaired spirometry.

BACKGROUND: Epidemiological evidence regarding the association between air pollutants and cardiopulmonary disease, mortality in individuals with preserved ratio impaired spirometry (PRISm), and their combined effects remains unclear. METHODS: We followed 36,149 participants with PRISm in the UK Biobank study. Annual concentrations of PM2.5, PM10, NO2, NOx, and SO2 at residential addresses were determined using a bilinear interpolation method, accounting for address changes. A multistate model assessed the dynamic associations between air pollutants and cardiopulmonary diseases and mortality in PRISm. Quantile g-computation was used to investigate the joint effects of air pollutants. RESULTS: Long-term exposure to PM2.5, PM10, NO2, NOx, and SO2 was significantly associated with the risk of cardiopulmonary disease in PRISm. The corresponding hazard ratios (HRs) [95 % confidence intervals (95 % CIs)] per interquartile range (IQR) were 1.49 (1.43, 1.54), 1.52 (1.46, 1.57), 1.34 (1.30, 1.39), 1.30 (1.26, 1.34), and 1.44 (1.41, 1.48), respectively. For mortality, the corresponding HRs (95 % CIs) per IQR were 1.36 (1.25, 1.47), 1.35 (1.24, 1.46), 1.27 (1.18, 1.36), 1.23 (1.15, 1.31), and 1.29 (1.20, 1.39), respectively. In PRISm, quantile g-computation analysis demonstrated that a quartile increase in exposure to a mixture of all air pollutants was positively associated with the risk of cardiopulmonary disease and mortality, with HRs (95 % CIs) of 1.84 (1.76, 3.84) and 1.45 (1.32, 1.57), respectively. CONCLUSION: Long-term individual and joint exposure to air pollutants (PM2.5, PM10, NO2, NOx, and SO2) might be an important risk factor for cardiopulmonary disease and mortality in high-risk populations with PRISm.

Short-term intermittent hypoxia exposure for dyspnea and fatigue in post-acute sequelae of COVID-19: A randomized controlled study.

BACKGROUND: Post-acute sequelae of COVID-19 (PASC) is incurring a huge health and economic burden worldwide. There is currently no effective treatment or recommended drug for PASC. METHODS: This prospective randomized controlled study was conducted in a hospital in China. The effect of intermittent hypoxia exposure (IHE; 5-min hypoxia alternating with 5-min normal air, repeated five times) on dyspnea and fatigue was investigated in patients meeting the NICE definition of PASC. Patients were computationally randomized to receive normoxia exposure (NE) and routine therapy or IHE and routine therapy. Six-minute walk distance (6MWD) and spirometry were tested before and after the interventions; the Borg Dyspnea Scale (Borg) and the modified Medical Research Council Dyspnea Scale (mMRC) were used to assess dyspnea; and the Fatigue Assessment Scale (FAS) and the Chalder Fatigue Scale-11 (CFQ-11) were used to assess fatigue. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300070565). FINDINGS: Ninety-five participants (33 males and 62 females) were recruited between March 1, 2023 and December 30, 2023. Forty-seven patients in the IHE group received 10.0 (9.0, 15.0) days of IHE, and 48 patients in NE group received 10.0 (8.0, 12.0) days of NE. 6MWD, forced vital capacity (FVC), FVC %pred, forced expiratory volume in 1 s (FEV1), FEV1 %pred, tidal volume (VT), and dyspnea and fatigue scales markedly improved after IHE (p < 0.05), and improvements were greater than in the NE group (all p < 0.05). Furthermore, participants in IHE group had better subjective improvements in dyspnea and fatigue than those in the NE group (p < 0.05). Compared with <10 days of IHE, ≥10 days of IHE had a greater impact on 6MWD, FVC, FEV1, FEV1 %pred, VT, FAS, and CFQ-11. No severe adverse events were reported. INTERPRETATION: IHE improved spirometry and 6MWD and relieved dyspnea and fatigue in PASC patients. Larger prospective studies are now needed to verify these findings.

Zoledronic Acid and Enriched Autologous Bone Marrow Stem Cell Implantation for Femoral Head Osteonecrosis.

Purpose: This study evaluated the clinical results of zoledronic acid in the treatment of early osteonecrosis of the femoral head (ONFH). Materials and Methods: Study retrospectively analyzed 60 patients with zoledronic acid with bone marrow stem cell (BMSC) implantation (The study group) and 64 patients with BMSC implantation (The control group). The primary evaluation index included VAS, HHS, collapsed rate, and total hip replacement arthroplasty (THA) conversion rate. Results: The study group had a lower VAS (1.12 ± 0.22 vs 1.44 ± 0.32) and higher HHS (75.07 ± 3.66 vs 68.78 ± 2.24) compared to the control group in 6 months after surgery (P < 0.05). In the study group, 12 hips (20%) collapsed, and 7 of 60 hips (11.67%) required THA surgery at the last follow-up. However, 25 hips (38.8%) collapsed in the control group, and 19 hips (29.69%) required THA surgery. The study group had a lower collapsed rate (P = 0.029) and THA conversion rate (P = 0.016) in survival analysis. Conclusion: Zoledronic acid and BMSC implantation in the treatment of early ONFH is safe and effective, reduces pain shortens recovery time, and reduces collapsed rate and THA conversion rate in ONFH patients.

Effects of modified oropharyngeal exercises on individuals with simple snoring: An online randomized controlled trial.

BACKGROUND: Individuals who suffer from simple snoring rarely go to a doctor due to a lack of medical knowledge, but simple snoring can reduce the individual's quality of life and may cause social problems to the bed partner/family members. OBJECTIVES: The aims of the present study are to explore the effects of online modified oropharyngeal exercises on the individuals with simple snoring and to provide a rehabilitation method for individuals with simple snoring. METHODS: This study is a double-blinded, two-arm, randomized controlled trial. Participants were enrolled and randomly assigned to the intervention group (n = 33) or the control group (n = 33). The participants in the control group received health education on snoring, while the participants in the intervention group received the modified oropharyngeal exercise besides health education on snoring. The intervention duration was 4 weeks. The primary outcomes included snoring index, snoring loudness, and snoring quantity. The secondary outcomes included self-reported snoring, sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life. All outcomes were measured at baseline, 4 weeks, and 8 weeks. RESULTS: Generalized estimating equations (GEE) analyses showed significant differences between the intervention group and the control group on snoring index, loudness, and quantity (p < .001). Moreover, modified oropharyngeal exercise had effects on sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life in individuals with simple snoring (p < .001). Self-reported snoring also improved at 8 weeks. CONCLUSION: The modified oropharyngeal exercises were effective in improving simple snoring. It could also improve sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life.

Multi-DECT image-based intratumoral and peritumoral radiomics for preoperative prediction of muscle invasion in bladder cancer.

OBJECTIVES: To assess the predictive value of intratumoral and peritumoral radiomics based on Dual-energy CT urography (DECTU) multi-images for preoperatively predicting the muscle invasion status of bladder cancer (BCa). MATERIAL AND METHODS: This retrospective analysis involved 202 BCa patients who underwent DECTU. DECTU-derived quantitative parameters were identified as risk factors through stepwise regression analysis to construct a DECT model. The radiomic features from the intratumoral and 3 mm outward peritumoral regions were extracted from the 120 kVp-like, 40 keV, 100 keV, and iodine-based material-decomposition (IMD) images in the venous-phase and were screened using Mann-Whitney U test, Spearman correlation analysis, and LASSO. Radiomics models were developed using the Multilayer Perceptron for the intratumoral, peritumoral and intra- and peritumoral (IntraPeri) regions. Subsequently, a nomogram was created by integrating the multi-image IntraPeri radiomics and DECT model. Model performance was evaluated using area-under-the-curve (AUC), accuracy, sensitivity, and specificity. RESULTS: Normalized iodine concentration (NIC) was identified as an independent predictor for the DECT model. The IntraPeri model demonstrated superior performance compared to the intratumoral and peritumoral models both in 40 keV (0.830 vs. 0.766 vs. 0.763) and IMD images (0.881 vs. 0.840 vs. 0.821) in the test cohort. In the test cohort, the nomogram exhibited the best predictability (AUC=0.886, accuracy=0.836, sensitivity=0.737, and specificity=0.881), outperformed the DECT model (AUC=0.763, accuracy=0.754, sensitivity=0.632, and specificity=0.810) in predicting muscle invasion status of BCa with a statistically significant difference (p < 0.05). CONCLUSION: The nomogram, incorporating IntraPeri radiomics and NIC, serves as a valuable and non-invasive tool for preoperatively assessing the muscle invasion status of BCa.

Water isotope ratios reflect convection intensity rather than rain type proportions in the pantropics.

Against the traditional view, a recently published theory argued that isotope ratios are higher in convective precipitation but lower in stratiform precipitation and proposed that isotope ratios reflect rain type proportions. This theory has been widely cited despite some early reservations. Whether the theory represents a faithful reflection of signals of water isotope ratios remains unclear. Here, we reassess its validity from different timescales and broader observations from the pantropics. Unexpectedly, our findings contradict the theory on daily, monthly, and even annual timescales. Pantropical precipitation isotope ratios remain strongly correlated to convection intensity but are independent of rain type proportions because stratiform precipitation isotope ratios cover a large range of values. We find that the theory has many serious weaknesses related to preferential data selection and suggest that new theories need to be validated at more locations on different timescales before gaining widespread acceptance.

Impact of multi-parameter images obtained from dual-energy CT on radiomics to predict pathological grading of bladder urothelial carcinoma.

OBJECTIVE: To investigate the effect of radiomics models obtained from dual-energy CT (DECT) material decomposition images and virtual monoenergetic images (VMIs) in predicting the pathological grading of bladder urothelial carcinoma (BUC). MATERIALS AND METHODS: A retrospective analysis of preoperative DECT examination was conducted on 112 patients diagnosed with BUC. This cohort included 76 cases of high-grade urothelial carcinoma and 36 cases of low-grade urothelial carcinoma. DECT can provide material decomposition images of venous phase Iodine maps and Water maps based on the differences in attenuation of substances, as well as VMIs at 40 to 140 keV (interval 10 keV). A total of 13 image sets were obtained, and radiomics features were extracted and analyzed from each set to achieve preoperative prediction of BUC. The best features related to BUC were identified by recursive feature elimination (RFE), the Minimum Redundancy Maximum Relevance (mRMR), and the Least Absolute Shrinkage and Selection Operator (LASSO) in order. A five-fold cross-validation method was used to divide the samples into training and testing sets, and models for pathological prediction of BUC grading were constructed by a random forest (RF) classifier. Receiver operating curves (ROC) were plotted to evaluate the performance of 13 models obtained from each image set. RESULTS: Despite the notable differences in the best radiomics features chosen from each image set, all the features selected from 40 to 100 keV VMIs included the Dependence Variance of the GLDM feature set. There were no statistically significant differences in the area under the curve (AUC) between the training set and the testing set for all 13 models. In the testing set, the AUCs of the models established through 40 keV to 140 keV (interval of 10 keV) image sets were 0.895, 0.874, 0.855, 0.889, 0.841, 0.868, 0.852, 0.847, 0.889, 0.887 and 0.863 respectively. The AUCs for the models established using the Iodine maps and Water maps image sets were 0.873 and 0.852, respectively. CONCLUSION: Despite the differences in the selected radiomic features from DECT multi-parameter images, the performance of radiomics models in predicting the pathological grading of BUC was not affected by the variations in the types of images used for model training.

Regulatory mechanisms orchestrating cellular diversity of Cd36+ olfactory sensory neurons revealed by scRNA-seq and scATAC-seq analysis.

Recent discoveries have revealed remarkable complexity within olfactory sensory neurons (OSNs), including the existence of two OSN populations based on the expression of Cd36. However, the regulatory mechanisms governing this cellular diversity in the same cell type remain elusive. Here, we show the preferential expression of 79 olfactory receptors in Cd36+ OSNs and the anterior projection characteristics of Cd36+ OSNs, indicating the non-randomness of Cd36 expression. The integrated analysis of single-cell RNA sequencing (scRNA-seq) and scATAC-seq reveals that the differences in Cd36+/- OSNs occur at the immature OSN stage, with Mef2a and Hdac9 being important regulators of developmental divergence. We hypothesize that the absence of Hdac9 may affect the activation of Mef2a, leading to the up-regulation of Mef2a target genes, including teashirt zinc finger family member 1 (Tshz1), in the Cd36+ OSN lineage. We validate that Tshz1 directly promotes Cd36 expression through enhancer bindings. Our study unravels the intricate regulatory landscape and principles governing cellular diversity in the olfactory system.

Synergistic removal of bio-recalcitrant organic compounds and nitrate: Coupling photocatalysis and biodegradation to enhance the bioavailability of electron donors.

Nitrate pollution poses significant threats to both aquatic ecosystems and human well-being, particularly due to eutrophication and increased risks of methemoglobinemia. Conventional treatment for nitrate-contaminated wastewater face challenges stemming from limited availability of carbon sources and the adverse impacts of toxins on denitrification processes. This study introduces an innovative Intimately Coupled Photocatalysis and Biodegradation (ICPB) system, which utilizes Ag3PO4/Bi4Ti3O12, denitrifying sludge, and polyurethane sponge within an anoxic environment. This system demonstrates remarkable efficacy in simultaneously removing bio-recalcitrant organic compounds (such as sulfamethoxazole) and nitrates, surpassing standalone treatment methods. Optimally, the ICPB achieves complete removal of sulfamethoxazole, along with 87.7 % removal of DOC, and 81.8 % reduction in nitrate levels. Its ability to sustain pollutant removal and biological activity over multiple cycles can be attributed to the special formation of biofilm and mineralization of sulfamethoxazole, minimizing both photocatalytic damage and toxic inhibitory effects on microbes. The dominant microbial genera of ICPB system included Castellaniella, Acidovorax, Raoultella, Giesbergeria, and Alicycliphilus. Additionally, the study sheds light on a potential mechanism for the concurrent treatment of recalcitrant organics and nitrates by the ICPB system, presenting a novel and highly effective approach for addressing biologically resistant wastewater.