Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure.

Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.

Tailoring the Ni-O Microenvironment in Amorphous-Dominated Highly Active and Stable Zn/NiO for Hydrogen Sulfide Detection.

Amorphous metal oxide semiconductor (MOS) materials are endowed with great promise to modulate electronic structures for gas-sensing performance improvement. However, the elevated-temperature requirement of gas sensors severely impedes the application of amorphous materials due to their low thermal stability. Here, a cationic-assisted strategy to tailor the Ni-O microenvironment in an amorphous-dominated Zn/NiO heterogeneous structure with high thermal stability was developed. It was found that 6 mol % Zn incorporation into amorphous NiO can effectively preserve the amorphous-dominated NiO phase even at high temperature. After calcination, the amorphous oxide can only be converted to crystals partly thus leading to the formation of amorphous/crystalline compounds, and the content of the amorphous phase can be adjusted by changing the calcination temperature. This amorphous/crystalline configuration can induce more electron transfer from Ni to Zn species, leading to the formation of active Niδ+ (δ>2) centers. Ex situ XPS and in situ Raman spectroscopy studies proved that the generated Niδ+ species pronouncedly promote the electron transfer during the H2S adsorption process. The amorphous/crystalline-6 mol % Zn/NiO sensor exhibits exceptional hydrogen sulfide response (2 ppm, 3.23), outstanding repeatability (as long as 5 weeks), and low limit of detection (as low as 50 ppb), surpassing most reported nickel-based gas sensors such as the crystal nickel oxide prepared in this work. The response and detection limit of the latter is only (2 ppm, 1.89) and (0.05 ppm) respectively. Our work thus opens up more opportunities for fundamental understanding and modulating of highly active amorphous sensing materials.

Increased C-Reactive Protein in Patients with Post-Stroke Depression: A Meta-analysis of Cohort Study.

Background: Pathophysiological mechanisms and related biological markers for post-stroke depression (PSD) are unknown. Some studies have noted that C-reactive protein (CRP) is activated in the serum of PSD patients. We aim to quantitatively summarize the concentrations of CRP in PSD patients compared to non-PSD patients. Methods: Original studies evaluating the association between CRP and PSD were searched in 4 specific databases from the establishment of the databases to March 2023. RevMan 5.20 and Stata 11.0 statistical software were used for meta-analysis. Publication bias was tested by Egger's test. The CRP level were combined by standardized mean difference (SMD) with 95% confidence interval (CI). Results: A total of 43 relevant literatures were retrieved, while 13 cohort studies were collected. The heterogeneity test result of the level of CRP in patients with PSD vs. non-PSD was (Q = 98.38, P < .001, I2 = 88%). The combined value of the estimated effect was [SMD = 0.34, 95% CI (0.12-0.56); P = .003]. Sensitivity analysis indicated that no study had a remarkable influence on the result of the pooled estimate. Egger's test was used to test the bias and the result was (Egger's test, P = .548), suggesting that there was no publication bias, and the results were credible. We found that different depression evaluation criteria (P = .035) and stroke types (P = .024) were considered as influencing factors for potential sources of heterogeneity. Conclusion: In conclusion, compared to those without depressive symptoms, patients with post-stroke depression have higher concentrations of CRP in the blood.

Kimura's Disease in Unusual Anatomical Locations: Clinical and Radiological Characteristics.

Purpose: To explore the clinical and imaging features of rare site Kimura's disease (KD). Methods: Retrospective analysis was conducted on the clinical manifestations, laboratory examinations, and imaging features of five patients with rare site KD. All imaging data, including the location, quantity, size, uniformity, boundary, and enhanced appearance of the lesion were evaluated by two independent radiologists. Results: Of the five patients, four were asymptomatic, and one experienced localized skin itching. Four cases involved subcutaneous nodules in the upper arm, while one was in the inguinal region. The main manifestations were single (three cases) or multiple (two cases) subcutaneous nodules/masses, with three patients accompanied by local lymph node enlargement. Four patients exhibited elevated eosinophil counts in their peripheral blood. Four patients had lesions with vascular flow voids; in three of these, the lesions also showed prominent enhancement. Notably, the lesion in a 5-year-old did not show vascular flow voids but displayed significant enhancement. Additionally, two patients showed edema around the lesions. Conclusion: The presence of solitary or multiple subcutaneous nodules/masses in the upper arm or inguinal area, accompanied by lymph node enlargement, elevated eosinophils in the peripheral blood, and the observation of internal vascular within the lesion, can aid in the diagnosis of KD occurring in uncommon anatomical locations.

Personalized Nanovaccines Enhance Lymph Node Accumulation and Reprogram the Tumor Microenvironment for Improved Photodynamic Immunotherapy.

Tumor immunotherapy has emerged as an efficacious therapeutic approach that mobilizes the patient's immune system to achieve durable tumor suppression. Here, we design a photodynamic therapy-motivated nanovaccine (Dex-HDL/ALA-Fe3O4) co-delivering 5-aminolevulinic acid and Fe3O4 nanozyme that demonstrate a long-term durable immunotherapy strategy. After vaccination, the nanovaccine exhibits obvious tumor site accumulation, lymph node homing, and specific and memory antitumor immunity evocation. Upon laser irradiation, Dex-HDL/ALA-Fe3O4 effectively generates reactive oxygen species at the tumor site not only to induce the immunogenic cell death-cascade but also to trigger the on-demand release of full types of tumor antigens. Intriguingly, Fe3O4 nanozyme-catalyzed hydrogen peroxide generated oxygen for alleviating tumor hypoxia and modifying the inhibitory tumor microenvironment, thereby exhibiting remarkable potential as a sensitizer. The intravenous administration of nanovaccines in diverse preclinical cancer models has demonstrated remarkable tumor regression and inhibition of postoperative tumor recurrence and metastasis, thereby enabling personalized treatment strategies against highly heterogeneous tumors.

Mechanochemical Vicinal Dibromination of Unactivated Alkenes and Alkynes Using Piezoelectric Material as a Redox Catalyst.

Mechanoredox chemistry is a rapidly evolving field at the intersection of mechanical forces and chemical reactions. Herein, we have reported a vicinal dibromination of unsaturated hydrocarbons using piezoelectric material (Li2TiO3) as a redox catalyst. Furthermore, the reaction can be efficiently scaled up to 10 mmol and performed under an air atmosphere at room temperature without solvents or external reductants, and Li2TiO3 can be reused multiple times without a structural change.

UHRF2 accumulates in early G1-phase after serum stimulation or mitotic exit to extend G1 and total cell cycle length.

Ubiquitin like with PHD and ring finger domains 2 (UHRF2) regulates the cell cycle and epigenetics as a multi-domain protein sharing homology with UHRF1. UHRF1 functions with DNMT1 to coordinate daughter strand methylation during DNA replication, but UHRF2 can't perform this function, and its roles during cell cycle progression are not well defined. UHRF2 role as an oncogene vs. tumor suppressor differs in distinct cell types. UHRF2 interacts with E2F1 to control Cyclin E1 (CCNE1) transcription. UHRF2 also functions in a reciprocal loop with Cyclin E/CDK2 during G1, first as a direct target of CDK2 phosphorylation, but also as an E3-ligase with direct activity toward both Cyclin E and Cyclin D. In this study, we demonstrate that UHRF2 is expressed in early G1 following either serum stimulation out of quiescence or in cells transiting directly out of M-phase, where UHRF2 protein is lost. Further, UHRF2 depletion in G2/M is reversed with a CDK1 specific inhibitor. UHRF2 controls expression levels of cyclins and CDK inhibitors and controls its own transcription in a negative-feedback loop. Deletion of UHRF2 using CRISPR/Cas9 caused a delay in passage through each cell cycle phase. UHRF2 loss culminated in elevated levels of cyclins but also the CDK inhibitor p27KIP1, which regulates G1 passage, to reduce retinoblastoma phosphorylation and increase the amount of time required to reach G1/S passage. Our data indicate that UHRF2 is a central regulator of cell-cycle pacing through its complex regulation of cell cycle gene expression and protein stability.

Functional type mediates the responses of root litter-driven priming effect and new carbon formation to warming.

Input of root litter can alter soil organic carbon (SOC) dynamics via causing priming effect (PE) on native SOC decomposition and forming new SOC. However, it is unknown how functional type mediates the root litter-driven PE and new C formation as well as their response to warming, which are of pivotal for soil C budget. We mixed litter segments of absorptive roots and transport roots from a Chinese fir (Cunninghamia lanceolata) plantation into isotopically distinct soil and incubated at 19°C (local mean annual temperature) and 23°C (warming by 4°C) for 210 days. Cumulative PE was calculated via integrating the instantaneous PE rates during the incubation. And the newly formed root litter-derived SOC (SOCrl) was calculated by measuring the δ13C value of soil at the end of incubation using a two-source mixed model. We found that absorptive roots with faster decomposition rates, caused significantly higher cumulative PE and SOCrl than transport roots. The microbial biomass and enzyme activities involved in C, N and P acquisition were significantly higher in the absorptive- than the transport roots addition treatment, indicating a higher level of microbial activation caused by absorptive roots. Although warming significantly increased the litter decomposition for both of functional types, while just significantly increased the PE of transport roots, indicating a root functional type dependent sensitivity of PE to warming. However, warming had no significant effect on SOCrl either for absorptive roots or for transport roots. As a consequence, warming relatively decreased the net SOC balance (difference between PE and SOCrl) in the transport roots addition treatment. Overall, our study highlights, for the first time, that functional type primarily mediates the response of root litter-driven PE to climate warming but not the new C formation, which may advance our understanding of SOC dynamics in Chinese fir plantation under climate change.

Above- and belowground phenology responses of subtropical Chinese fir (Cunninghamia lanceolata) to soil warming, precipitation exclusion and their interaction.

Plant phenology plays an important role in nutrient cycling and carbon balance in forest ecosystems, but its response to the interaction of global warming and precipitation reduction remains unclear. In this study, an experiment with factorial soil warming (ambient, ambient +5 °C) and precipitation exclusion (ambient, ambient -50 %) was conducted in a subtropical Chinese fir (Cunninghamia lanceolata) plantation. We investigated the effects of soil warming, precipitation exclusion, and their interactions on Chinese fir phenology involving tree height and fine root growth. In the meantime, the impact of tree height growth and related climatic factors on fine root production was also assessed. The results showed that: (1) more variable phenology responses were observed in fine root growth than in tree height growth to the climatic treatments; the duration of fine root growth and tree height growth was significantly reduced by the precipitation exclusion and warming treatment, respectively; phenology differences of fine root and tree height growth caused by the solo warming and precipitation exclusion treatment were further enhanced by the combined treatment; and despite the greater inter-annual phenology stability of tree height growth than that of fine root growth, both of them showed insignificant response to all the climate treatments; (2) asynchrony of phenology between tree height and fine root growth was significantly enlarged by solo warming and precipitation exclusion treatments, and further enlarged by the combined treatment; (3) fine root production was significantly and positively correlated with air, and soil temperature, and tree height growth as well, which was altered by warming and precipitation exclusion treatments. Our results demonstrated that climatic changes significantly and differently alter phenology of, and extend the phenology asynchrony between, above and below ground plant components, and also highlight the climate-sensitive and variable nature of root phenology. Overall, these phenology responses to climatic change may weaken the close link between fine root production and tree height growth, which may result in temporal mismatch between nutrient demand and supply in Chinese fir plantation.

Deciphering the therapeutic potential of SheXiangXinTongNing: Interplay between gut microbiota and brain metabolomics in a CUMS mice model, with a focus on tryptophan metabolism.

Depression, a prevalent and multifaceted mental disorder, has emerged as a significant public health concern due to its escalating prevalence and heightened risk of severe suicidality. Given its profound impact, the imperative for preventing and intervening in depression is paramount. Substantial evidence underscores intricate connections between depression and cardiovascular health. SheXiangXinTongNing (XTN), a recognized traditional Chinese medicine for treating Coronary Heart Disease (CHD), prompted our exploration into its antidepressant effects and underlying mechanisms. In this investigation, we assessed XTN's antidepressant potential using the chronic unpredictable mild stress (CUMS) mice model and behavioral tests. Employing network pharmacology, we delved into the intricate mechanisms at play. We characterized the microbial composition and function in CUMS mice, both with and without XTN treatment, utilizing 16S rRNA sequencing and metabolomics analysis. The joint analysis of these results via Cytoscape identified pivotal metabolic pathways. In the realm of network pharmacology, XTN administration exhibited antidepressant effects by modulating pathways such as IL-17, neuroactive ligand-receptor interaction, PI3K-Akt, cAMP, calcium, and dopamine synapse signaling pathways. Our findings revealed that XTN significantly mitigated depression-like symptoms and cognitive deficits in CUMS mice by inhibiting neuroinflammation and pyroptosis. Furthermore, 16S rRNA sequencing unveiled that XTN increased the alpha-diversity and beta-diversity of the gut microbiome in CUMS mice. Metabolomics analysis identified brain metabolites crucial for distinguishing between the CUMS and CUMS+XTN groups, with a focus on pathways like Tryptophan metabolism and Linoleic acid metabolism. Notably, specific bacterial families, including Alloprevotella, Helicobacter, Allobaculum, and Clostridia, exhibited robust co-occurring relationships with brain tryptophan metabolomics, hinting at the potential mediating role of gut microbiome alterations and metabolites in the efficacy of XTN treatment. In conclusion, our study unveils modifications in microbial compositions and metabolic functions may be pivotal in understanding the response to XTN treatment, offering novel insights into the mechanisms underpinning the efficacy of antidepressants.

Cholesterol neutralized vemurafenib treatment by promoting melanoma stem-like cells via its metabolite 27-hydroxycholesterol.

Vemurafenib has been used as first-line therapy for unresectable or metastatic melanoma with BRAFV600E mutation. However, overall survival is still limited due to treatment resistance after about one year. Therefore, identifying new therapeutic targets for melanoma is crucial for improving clinical outcomes. In the present study, we found that lowering intracellular cholesterol by knocking down DHCR24, the limiting synthetase, impaired tumor cell proliferation and migration and abrogated the ability to xenotransplant tumors. More importantly, administration of DHCR24 or cholesterol mediated resistance to vemurafenib and promoted the growth of melanoma spheroids. Mechanistically, we identified that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol synthesized by the enzyme cytochrome P450 27A1 (CYP27A1), reproduces the phenotypes induced by DHCR24 or cholesterol administration and activates Rap1-PI3K/AKT signaling. Accordingly, CYP27A1 is highly expressed in melanoma patients and upregulated by DHCR24 induction. Dafadine-A, a CYP27A1 inhibitor, attenuates cholesterol-induced growth of melanoma spheroids and abrogates the resistance property of vemurafenib-resistant melanoma cells. Finally, we confirmed that the effects of cholesterol on melanoma resistance require its metabolite 27HC through CYP27A1 catalysis, and that 27HC further upregulates Rap1A/Rap1B expression and increases AKT phosphorylation. Thus, our results suggest that targeting 27HC may be a useful strategy to overcome treatment resistance in metastatic melanoma.

Construction of a pH- and viscosity-switchable near-infrared fluorescent probe and its imaging application.

Viscosity is a parameter used to measure the fluidity of liquids and a key indicator in evaluating the states of body fluid in biological tissues and lesions. Most traditional detection methods have many drawbacks such as a short emission wavelength and interference by background fluorescence. Inspired by the multiple double bond structure of retinal, a novel pH and viscosity dual-response fluorescent probe (Rh-TR) was constructed in this study. Rh-TR exhibited two emission signals centered at 510 and 660 nm. As the pH of the phosphate-buffered saline increased, the fluorescence at 510 nm increased by about 124-fold, while the change in fluorescence at 660 nm was not obvious. When detecting the change in viscosity using the probe, the fluorescence at 510 nm decreased by about 85 %, while the fluorescence at 660 nm increased by over 20-fold. The probe also showed high selectivity and little toxicity. As demonstrated by the biological imaging experiment, the probe successfully imaged changes in the pH and viscosity of cells and in a live animal model of zebrafish. Considering the unique structure of Rh-TR with retinal and its pH- and viscosity-switchable spectral property, the probe may find further application in detecting viscosity-related diseases and industrial detection.

An Innovative and Efficient Fluorescent Detection Technique for Salmonella in Animal-Derived Foods Using the CRISPR/Cas12a-HCR System Combined with PCR/RAA.

Here, we present a method for Salmonella detection using clustered regularly interspaced short palindromic repeats associated with the CRISPR-associated protein 12a-hybridization chain reaction (CRISPR/Cas12a-HCR) system combined with polymerase chain reaction/recombinase-assisted amplification (PCR/RAA) technology. The approach relies on the Salmonella invA gene as a biorecognition element and its amplification through PCR and RAA. In the presence of the target gene, Cas12a, guided by crRNA, recognizes and cleaves the amplification product, initiating the HCR. Fluorescently labeled single-stranded DNA (ssDNA) H1 and H2 were introduced, and the Salmonella concentration was determined based on the fluorescence intensity from the triggered HCR. Both assays demonstrate high specificity, sensitivity, simplicity, and rapidity. The detection range was 2 × 101-2 × 109 CFU/mL, with an LOD of 20 CFU/mL, and the entire process enabled specific and rapid Salmonella detection within 85-105 min. Field-incurred spiked recovery tests were conducted in mutton and beef samples using both assays, demonstrating satisfactory recovery and accuracy in animal-derived foods. By combining CRISPR/Cas12a with hybridization chain reaction technology, this study presents a rapid and sensitive Salmonella detection method that is crucial for identifying pathogenic bacteria and monitoring food safety.

KMT2C mutation as a predictor of immunotherapeutic efficacy in colorectal cancer.

Immunotherapy had shown good antitumor activity in a variety of solid tumors, but low benefit in CRC, so there was an urgent need to explore new biomarkers. We evaluated the role of KMT2C using publicly available data from the Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC). In addition, further analysis was performed in an internal cohort. Moreover, the mutant profiles of KMT2C was analyzed in a large CRC cohort. The relationship between clinical pathologic features and KMT2C were analyzed with using the two-sided chi-squared test or the Fisher exact test. Clinicopathologic characteristics associated with overall survival using Cox regression and the Kaplan-Meier method. We found that KMT2C-mutated CRC patients in the immunotherapy cohort had significantly improved OS compared with KMT2C WT patients (P = 0.013). However, this phenomenon did not exist in non-immunotherapy cohort. Our cohort validated the value of KMT2C mutations in predicting better clinical outcomes, including ORR (P < 0.0001) and OS (P = 0.010). Meanwhile, KMT2C mutation was associated with higher tumor mutation burden, MSI score, higher levels of immune-associated T cells, neutrophil, and M1-type macrophages. Our study suggested that KMT2C mutation might be a potential positive predictor for CRC immunotherapy.

Synthesis of ß-Cyclodextrin@gold Nanoparticles and Its Application on Colorimetric Assays for Ascorbic Acid and Salmonella Based on Peroxidase-like Activities.

The peroxidase-like behaviors of gold nanoparticles (AuNPs) have the potential to the development of rapid and sensitive colorimetric assays for specific food ingredients and contaminants. Here, using NaBH4 as a reducing agent, AuNPs with a supramolecular macrocyclic compound ß-cyclodextrin (ß-CD) capped were synthesized under alkaline conditions. Monodispersal of ß-CD@AuNPs possessed a reduction in diameter size and performed great peroxidase-like activities toward both substrates, H2O2 and TMB. In the presence of H2O2, the color change of TMB oxidization to oxTMB was well-achieved using ß-CD@AuNPs as the catalyst, which was further employed to develop colorimetric assays for ascorbic acid, with a limit of detection as low as 0.2 µM in ddH2O. With the help of the host-guest interaction between ß-CD and adamantane, AuNPs conjugated with nanobodies to exhibit peroxidase-like activities and specific recognition against Salmonella Typhimurium simultaneously. Based on this bifunctional bioprobe, a selective and sensitive one-step colorimetric assay for S. Typhimurium was developed with a linear detection from 8.3 × 104 to 2.6 × 108 CFU/mL and can be provided to spiked lettuce with acceptable recoveries of 97.31% to 103.29%. The results demonstrated that the excellent peroxidase-like behaviors of ß-CD@AuNPs can be applied to develop a colorimetric sensing platform in the food industry.

Effect of glycotoxicity and lipotoxicity on carbohydrate antigen 19 - 9 in the patients with diabetes.

OBJECTIVES: In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 - 9 (CA 19 - 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 - 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 - 9 in hospitalized patients with diabetes was the focus of our research. METHOD: A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. RESULTS: We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c < 9% group, 2.5% in the control group. There was no significant difference in the HbA1c < 9% group and the control group. A significant correlation between serum CA19-9 and both HbA1c and total cholesterol was observed, yet no difference in CRP level was observed between subjects with normal CA19-9 level and subjects with abnormal CA19-9 level. However, a significant difference in fasting C-peptide levels was observed between the two groups, p = 0.039. CONCLUSION: The percentage of patients with diabetes exhibiting elevated CA19-9 level is 14% in the HbA1c ≥ 9% diabetic patients, much higher than expected. The underlying mechanism may be related to islet injury caused by glycotoxicity and lipotoxicity. STRENGTHS AND LIMITATIONS OF THE STUDY: We studied the rate of hospitalized diabetic patients with elevated CA 19 - 9 which were characterized with poorly controlled blood glucose. We found that the elevation of CA 19 - 9 was unexpectedly high in diabetic inpatients without development to cancer. The limitation of this study is that the underlying mechanism is not sufficiently studied.

Correction: Effect of support on hydrogen generation over iron oxides in the chemical looping process.

[This corrects the article DOI: 10.1039/D1RA07210B.].

Screening and Diagnosis of Rare Thalassemia Variants: Is Third-Generation Sequencing Enough?

CONTEXT.­: Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and ß-thalassemia. OBJECTIVE.­: To assess a comprehensive approach for the screening and diagnosis of rare thalassemia. DESIGN.­: The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing. RESULTS.­: Of the 72 individuals with suspected rare thalassemia, 49 had rare α- or ß-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the ß41-42/ßN and ßN/ßN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified. CONCLUSIONS.­: Rare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.

KIF11 UFMylation Maintains Photoreceptor Cilium Integrity and Retinal Homeostasis.

The photoreceptor cilium is vital for maintaining the structure and function of the retina. However, the molecular mechanisms underlying the photoreceptor cilium integrity and retinal homeostasis are largely unknown. Herein, it is shown that kinesin family member 11 (KIF11) localizes at the transition zone (connecting cilium) of the photoreceptor and plays a crucial role in orchestrating the cilium integrity. KIF11 depletion causes malformations of both the photoreceptor ciliary axoneme and membranous discs, resulting in photoreceptor degeneration and the accumulation of drusen-like deposits throughout the retina. Mechanistic studies show that the stability of KIF11 is regulated by an interplay between its UFMylation and ubiquitination; UFMylation of KIF11 at lysine 953 inhibits its ubiquitination by synoviolin 1 and thereby prevents its proteasomal degradation. The lysine 953-to-arginine mutant of KIF11 is more stable than wild-type KIF11 and also more effective in reversing the ciliary and retinal defects induced by KIF11 depletion. These findings identify a critical role for KIF11 UFMylation in the maintenance of photoreceptor cilium integrity and retinal homeostasis.

Soil microbes deal with the nitrogen deposition enhanced phosphorus limitation by shifting community structure in an old-growth subtropical forest.

Elevated atmospheric nitrogen (N) deposition potentially enhances the degree of phosphorus (P) limitation in tropical and subtropical forests. However, it remains elusive that how soil microorganisms deal with the N deposition-enhanced P limitation. We collected soils experienced 9 years of manipulative N input at various rates (0, 40, and 80 kg N ha-1 y-1) in an old-growth subtropical natural forest. We measured soil total and available carbon (C), N and P, microbial biomass C, N and P, enzyme activities involved in C, N and P acquisition, microbial community structure, as well as net N and P mineralization. Additionally, we calculated element use efficiency and evaluated microbial homeostasis index. Our findings revealed that N input increased microbial biomass C:P (MBC:P) and N:P (MBN:P) ratios. The homeostasis indexes of MBC:P and MBN:P were 0.68 and 0.75, respectively, indicating stoichiometric flexibility. Interestingly, MBC:P and MBN:P correlated significantly with the fungi:bacteria ratio (F:B), not with N and P use efficiencies, net N and P mineralization, and enzyme C:P (EEAC:P) and N:P (EEAN:P) ratios. Furthermore, EEAC:P and EEAN:P correlated positively with F:B but did not negatively correlate with the C:P and N:P ratios of available resources and microbial biomass. The effects of N deposition on MBC:P, MBN:P and EEAN:P became insignificant when including F:B as a covariate. These findings suggest that microbes flexibly adapted to the N deposition enhanced P limitation by changing microbial community structure, which not only alter microbial biomass C:N:P stoichiometry, but also the enzyme production strategy. In summary, our research advances our understanding of how soil microorganisms deal with the N deposition-enhanced soil P limitation in subtropical forests.