Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism.

Nowadays, presynaptic dopaminergic positron emission tomography, which assesses deficiencies in dopamine synthesis, storage, and transport, is widely utilized for early diagnosis and differential diagnosis of parkinsonism. This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism. We conducted a thorough literature search using reputable databases such as PubMed and Web of Science. Selection criteria involved identifying peer-reviewed articles published within the last 5 years, with emphasis on their relevance to clinical applications. The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis. Moreover, when employed in conjunction with other imaging modalities and advanced analytical methods, presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker. This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion. In summary, the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials, ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

l-Carnosine loaded on carboxymethyl cellulose hydrogels for promoting wound healing.

Wound management remains a challenge in clinical practice. Nowadays, patients have an increasing demand for wound repair with enhanced speed and quality; therefore, there is a great need to seek therapeutic strategies that can promote rapid and effective wound healing. In this study, we developed a carboxymethyl cellulose hydrogel loaded with l-carnosine (CRN@hydrogel) for potential application as a wound dressing. In vitro experiments confirmed that CRN@hydrogel can release over 80% of the drug within 48 h and demonstrated its favorable cytocompatibility and blood compatibility, thus establishing its applicability for safe utilization in clinical practice. Using a rat model, we found that this hydrogel could promote and accelerate wound healing more effectively. These results indicate that the novel hydrogel can serve as an efficient therapeutic strategy for wound treatment.

Imaging neuroinflammation in individuals with substance use disorders.

Increasing evidence suggests a role of neuroinflammation in substance use disorders (SUDs). This Review presents findings from neuroimaging studies assessing brain markers of inflammation in vivo in individuals with SUDs. Most studies investigated the translocator protein 18 kDa (TSPO) using PET; neuroimmune markers myo-inositol, choline-containing compounds, and N-acetyl aspartate using magnetic resonance spectroscopy; and fractional anisotropy using MRI. Study findings have contributed to a greater understanding of neuroimmune function in the pathophysiology of SUDs, including its temporal dynamics (i.e., acute versus chronic substance use) and new targets for SUD treatment.

Unveiling novel cell clusters and biomarkers in glioblastoma and its peritumoral microenvironment at the single-cell perspective.

BACKGROUND: Glioblastoma (GBM) is a highly heterogeneous, recurrent and aggressively invasive primary malignant brain tumor. The heterogeneity of GBM results in poor targeted therapy. Therefore, the aim of this study is to depict the cellular landscape of GBM and its peritumor from a single-cell perspective. Discovering new cell subtypes and biomarkers, and providing a theoretical basis for precision therapy. METHODS: We collected 8 tissue samples from 4 GBM patients to perform 10 × single-cell transcriptome sequencing. Quality control and filtering of data by Seurat package for clustering. Inferring copy number variations to identify malignant cells via the infercnv package. Functional enrichment analysis was performed by GSVA and clusterProfiler packages. STRING database and Cytoscape software were used to construct protein interaction networks. Inferring transcription factors by pySCENIC. Building cell differentiation trajectories via the monocle package. To infer intercellular communication networks by CellPhoneDB software. RESULTS: We observed that the tumor microenvironment (TME) varies among different locations and different GBM patients. We identified a proliferative cluster of oligodendrocytes with high expression of mitochondrial genes. We also identified two clusters of myeloid cells, one primarily located in the peritumor exhibiting an M1 phenotype with elevated TNFAIP8L3 expression, and another in the tumor and peritumor showing a proliferative tendency towards an M2 phenotype with increased DTL expression. We identified XIST, KCNH7, SYT1 and DIAPH3 as potential factors associated with the proliferation of malignant cells in GBM. CONCLUSIONS: These biomarkers and cell clusters we discovered may serve as targets for treatment. Targeted drugs developed against these biomarkers and cell clusters may enhance treatment efficacy, optimize immune therapy strategies, and improve the response rates of GBM patients to immunotherapy. Our findings provide a theoretical basis for the development of individualized treatment and precision medicine for GBM, which may be used to improve the survival of GBM patients.

Genetic variations of low-density lipoprotein cholesterol on metabolic disorders in obstructive sleep apnea.

BACKGROUND: The study aimed to explore the relationship between low-density lipoprotein cholesterol (LDL-C) genetic variants and obstructive sleep apnea (OSA) and its complications, including cardiovascular diseases (CVD), insulin resistance (IR), and metabolic syndrome (MS). METHOD: 4329 individuals with suspected OSA who underwent a comprehensive assessment of anthropometric, biochemical, and polysomnography (PSG) data, along with 30 LDL-C single nucleotide polymorphisms (SNPs) were enrolled. The 10-year Framingham CVD risk score (FRS), IR and MS were evaluated for each subject. Linear regression and logistic regression were utilized to examine the correlations among these variables. RESULTS: After the Benjamini-Hochberg correction, linear regression results indicated positive correlations between variants rs3741297 and rs629301 with FRS (ß = 0.031, PBH=0.002; ß = 0.026, PBH=0.015). Logistic regression revealed that rs3741297 increased MS risk among total subjects [OR = 1.67 (95% CI:1.369-2.038), PBH=1.32 × 10- 5] and increased IR risk in females [OR = 3.475 (95% CI:1.653-7.307), PBH=0.03]. In males, rs2642438 decreased MS risk [OR = 0.81 (95% CI:0.703-0.933), PBH=0.045]. CONCLUSIONS: The rs3741297 variant correlated with susceptibility to CVD, IR, and MS in the OSA population. OSA, CVD, IR and MS share a potentially common genetic background, which may promote precision medicine. CINICAL TRIAL REGISTRATION: The study protocol was registered with the Chinese Clinical Trial Registry (ChiCTR1900025714).

PR-SET7 epigenetically restrains uterine interferon response and cell death governing proper postnatal stromal development.

The differentiation of the stroma is a hallmark event during postnatal uterine development. However, the spatiotemporal changes that occur during this process and the underlying regulatory mechanisms remain elusive. Here, we comprehensively delineated the dynamic development of the neonatal uterus at single-cell resolution and characterized two distinct stromal subpopulations, inner and outer stroma. Furthermore, single-cell RNA sequencing revealed that uterine ablation of Pr-set7, the sole methyltransferase catalyzing H4K20me1, led to a reduced proportion of the inner stroma due to massive cell death, thus impeding uterine development. By combining RNA sequencing and epigenetic profiling of H4K20me1, we demonstrated that PR-SET7-H4K20me1 either directly repressed the transcription of interferon stimulated genes or indirectly restricted the interferon response via silencing endogenous retroviruses. Declined H4K20me1 level caused viral mimicry responses and ZBP1-mediated apoptosis and necroptosis in stromal cells. Collectively, our study provides insight into the epigenetic machinery governing postnatal uterine stromal development mediated by PR-SET7.

From waste to strength: Tailor-made enzyme activation design transformation of denatured soy meal into high-performance all-biomass adhesive.

Given the severe protein denaturation and self-aggregation during the high-temperature desolubilization, denatured soy meal (DSM) is limited by its low reactivity, high viscosity, and poor water solubility. Preparing low-cost and high-performance adhesives with DSM as the key feedstock is still challenging. Herein, this study reveals a double-enzyme co-activation method targeting DSM with the glycosidic bonds in protein-carbohydrate complexes and partial amide bonds in protein, increasing the protein dispersion index from 10.2 % to 75.1 % improves the reactivity of DSM. The green crosslinker transglutaminase (TGase) constructs a robust adhesive isopeptide bond network with high water-resistant bonding strength comparable to chemical crosslinkers. The adhesive has demonstrated high dry/wet shear strength (2.56 and 0.93 MPa) for plywood. After molecular recombination by enzyme strategy, the adhesive had the proper viscosity, high reactivity, and strong water resistance. This research showcases a novel perspective on developing a DSM-based adhesive and blazes new avenues for changes in protein structural function and adhesive performance.

Fetal liver CD34+ contain human immune and endothelial progenitors and mediate solid tumor rejection in NOG mice.

BACKGROUND: Transplantation of CD34+ hematopoietic stem and progenitor cells (HSPC) into immunodeficient mice is an established method to generate humanized mice harbouring a human immune system. Different sources and methods for CD34+ isolation have been employed by various research groups, resulting in customized models that are difficult to compare. A more detailed characterization of CD34+ isolates is needed for a better understanding of engraftable hematopoietic and potentially non-hematopoietic cells. Here we have performed a direct comparison of CD34+ isolated from cord blood (CB-CD34+) or fetal liver (FL-CD34+ and FL-CD34+CD14-) and their engraftment into immunocompromised NOD/Shi-scid Il2rgnull (NOG) mice. METHODS: NOG mice were transplanted with either CB-CD34+, FL-CD34+ or FL-CD34+CD14- to generate CB-NOG, FL-NOG and FL-CD14--NOG, respectively. After 15-20 weeks, the mice were sacrificed and human immune cell reconstitution was assessed in blood and several organs. Liver sections were pathologically assessed upon Haematoxylin and Eosin staining. To assess the capability of allogenic tumor rejection in CB- vs. FL-reconstituted mice, animals were subcutaneously engrafted with an HLA-mismatched melanoma cell line. Tumor growth was assessed by calliper measurements and a Luminex-based assay was used to compare the cytokine/chemokine profiles. RESULTS: We show that CB-CD34+ are a uniform population of HSPC that reconstitute NOG mice more rapidly than FL-CD34+ due to faster B cell development. However, upon long-term engraftment, FL-NOG display increased numbers of neutrophils, dendritic cells and macrophages in multiple tissues. In addition to HSPC, FL-CD34+ isolates contain non-hematopoietic CD14+ endothelial cells that enhance the engraftment of the human immune system in FL-NOG mice. We demonstrate that these CD14+CD34+ cells are capable of reconstituting Factor VIII-producing liver sinusoidal endothelial cells (LSEC) in FL-NOG. However, CD14+CD34+ also contribute to hepatic sinusoidal dilatation and immune cell infiltration, which may culminate in a graft-versus-host disease (GVHD) pathology upon long-term engraftment. Finally, using an HLA-A mismatched CDX melanoma model, we show that FL-NOG, but not CB-NOG, can mount a graft-versus-tumor (GVT) response resulting in tumor rejection. CONCLUSION: Our results highlight important phenotypical and functional differences between CB- and FL-NOG and reveal FL-NOG as a potential model to study hepatic sinusoidal dilatation and mechanisms of GVT.

Soluble CXCL16 is a prognostic biomarker associated with rapidly progressive interstitial lung disease complicated with dermatomyositis.

OBJECTIVES: Rapidly progressive interstitial lung disease (RPILD) in patients with dermatomyositis (DM) significantly impacts prognosis, leading to high mortality rates. Although several indicators have been demonstrated to strongly correlate with the risk of developing RPILD, their clinical utility still needs to be investigated. The objective of this study was to investigate the clinical significance of soluble CXCL16 (sCXCL16) in DM patients complicated with RPILD. METHODS: Serum sCXCL16 was measured by enzyme-linked immunosorbent assay in 96 patients with DM and 55 matching healthy donors. Correlations between sCXCL16 levels and clinical features, laboratory examinations and the predictive value of baseline sCXCL16 level for RPILD were analysed. RESULTS: The serum sCXCL16 levels were significantly higher in patients with DM (n = 96, 3.264 ± 1.516 ng/mL) compared with healthy donors (n = 55, 1.781 ± 0.318 ng/mL), especially in DM complicated with RPILD (n = 31, 4.441 ± 1.706 ng/mL). The sCXCL16 levels were positively correlated with levels of serum ferritin, C reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, hydroxybutyrate dehydrogenase, and negatively correlated with peripheral lymphocytes percentage, but showed no correlation with levels of anti-melanoma differentiation-associated gene 5 antibody, Krebs von den Lungen-6 or creatine kinase. Multivariable analysis showed that elevated sCXCL16 was an independent prognostic factor for poor prognosis of RPILD in patients with DM. The 2-year survival rate was significantly lower in patients with high sCXCL16 level than in those with low sCXCL16 level. CONCLUSION: A higher serum sCXCL16 level was identified as a predictive biomarker of RPILD in patients with DM, and closely associated with poor prognosis.

Gut microbiome changes associated with chronic pancreatitis and pancreatic cancer: A systematic review and Meta-analysis.

BACKGROUND: The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC. METHODS: Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes we focus on. RESULTS: This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC (n=285), CP (n=342), and control (n=649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=-0.33; P=0.002 and SMD=-0.59; P<0.001, respectively) and a statistically significant ß-diversity (P<0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that 4 genera were significantly increased in PDAC patients compared to HC (e.g., Escherichia-Shigella and Veillonella). CP patients had an increase in 4 genera (e.g., Escherichia-Shigella and Klebsiella) and a decrease in 8 genera (e.g., Coprococcus and Bifidobacterium) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients. CONCLUSIONS: Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.

A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders.

Background: Patent foramen ovale (PFO) has a genetic predisposition and is closely associated with cryptogenic stroke (CS), migraine, decompression sickness, and hypoxemia. Identifying PFO-related mutant genes through whole-exome sequencing (WES) can help in the early recognition of cardiovascular genetic risk factors, guide timely clinical intervention, and reduce the occurrence of cardiovascular events. Methods: We analyzed mutant genes from ClinVar and OMIM databases. WES was performed on 25 PFO patients from Zhejiang Provincial Hospital of Chinese Medicine. Pathogenicity of variants was evaluated using American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology. (AMP) guidelines. Results: In ClinVar (4 Feb 2023), 113 coding gene mutations were found, including 83 associated with PFO. From OMIM (18 Apr 2023), 184 gene mutations were analyzed, with 110 mutant coding genes. WES identified pathogenic mutations in two of 25 PFO patients (8%). LDLR, SDHC, and NKX2-5 genes were linked to PFO and primarily involved in myocardial tissue function. NKX2-5 may play a crucial role in PFO development, interacting with NOTCH1, GATA4, MYH6, SCN5A signaling pathways regulating cardiomyocyte characteristics. Conclusion: We identified pathogenic mutations in LDLR, SDHC, and NKX2-5 genes, implying their role in PFO development. Functional enrichment analysis revealed NKX2-5's interaction with signaling pathways regulating cardiomyocyte function. These findings enhance our understanding of PFO's genetic basis, suggesting potential therapeutic targets for future research.

Influence of grandchildren on COVID-19 vaccination uptake among older adults in China: a parallel-group, cluster-randomized controlled trial.

The uptake of COVID-19 booster vaccination among older adults in China is suboptimal. Here, we report the results of a parallel-group cluster-randomized controlled trial evaluating the efficacy of promoting COVID-19 booster vaccination among grandparents (≥60 years) through a health education intervention delivered to their grandchildren (aged ≥16 years) in a Chinese cohort (Chinese Clinical Trial Registry: ChiCTR2200063240 ). The primary outcome was the uptake rate of COVID-19 booster dose among grandparents. Secondary outcomes include grandparents' attitude and intention to get a COVID-19 booster dose. A total of 202 college students were randomized 1:1 to either the intervention arm of web-based health education and 14 daily reminders (n = 188 grandparents) or control arm (n = 187 grandparents) and reported their grandparents' COVID-19 booster vaccination status at baseline and 21 days. Grandparents in the intervention arm were more likely to receive COVID-19 booster vaccination compared to control cohort (intervention, 30.6%; control, 16.9%; risk ratio = 2.00 (95% CI, 1.09 to 3.66)). Grandparents in the intervention arm also had greater attitude change (ß = 0.28 (95% CI, 0.04 to 0.52)) and intention change (ß = 0.32 (95% CI, 0.12 to 0.52)) to receive a COVID-19 booster dose. Our results show that an educational intervention targeting college students increased COVID-19 booster vaccination uptake among grandparents in China.

Da-yuan-yin decoction alleviates ulcerative colitis by inhibiting complement activation, LPS-TLR4/NF-κB signaling pathway and NET formation.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-yuan-yin decoction (DYY) is a classical traditional Chinese medicine prescription for ulcerative colitis (UC). AIM OF STUDY: This study explored the protective effects and mechanisms of DYY on UC. MATERIALS AND METHODS: The mice were fed 2.5% dextran sulfate sodium (DSS) for 7 days to establish UC. On the second day, DYY (0.4 g/kg, 0.8 g/kg, 1.6 g/kg) was orally administered daily for 7 consecutive days. The colon tissues and serum were measured by histopathological examination and biochemical analysis. RESULTS: DYY significantly reduced the disease activity index (DAI) and severity of colon shortening and alleviated pathological changes in the colon tissue. DYY restored the protein expression of intestinal tight junction (TJ) protein (ZO-1, occludin and claudin-3). DYY remarkably decreased the level of lipopolysaccharide (LPS), Lactic acid (LA), circulating free DNA (cfDNA), complement (C3, C3a, C3c, C3aR1, C5a and C5aR1) and regulated the levels of inflammatory cytokines in serum. DYY significantly inhibited the expressions of nuclear factor kappa-B p65 (NF-κB p65) and Toll-like receptor 4 (TLR4), citrullinated histone H3 (CitH3) and myeloperoxidase (MPO), reactive oxygen species (ROS) peptidylarginine deiminase 4 (PAD4) and CD 11b, the mRNA levels of PADI4, MPO and ELANE in colon tissues. CONCLUSIONS: DYY significantly attenuated DSS-induced UC, which was related with regulating the inflammatory response by the inhibition of complement activation, the LPS-TLR4/NF-κB signaling pathway and neutrophil extracellular traps (NETs) formation. DYY is a potential therapeutic agent for UC.

Impacts of preparation technologies on biological activities of edible mushroom polysaccharides - novel insights for personalized nutrition achievement.

Edible mushroom polysaccharides (EMPs) as a natural macromolecular carbohydrate have a very complex structure and composition. EMPs are considered ideal candidates for developing healthy products and functional foods and have received significant research attention due to their unique physiological activities such as immunomodulatory, anti-inflammatory, anti-tumor/cancer, gut microbiota regulation, metabolism improvement, and nervous system protection. The structure and monosaccharide composition of edible mushroom polysaccharides have an unknown relationship with their functional activity, which has not been widely studied. Therefore, we summarized the preparation techniques of EMPs and discussed the association between functional activity, preparation methods, structure and composition of EMPs, laying a theoretical foundation for the personalized nutritional achievements of EMP. We also establish the foundation for the further investigation and application of EMPs as novel functional foods and healthy products.

Effects of toothpaste containing inactivated Lacticaseibacillus paracasei Probio-01 on plaque-induced gingivitis and dental plaque microbiota.

Plaque-induced gingivitis is an inflammatory response in gingival tissues resulting from bacterial plaque accumulation at the gingival margin. Postbiotics can promote the proliferation of beneficial bacteria and optimise the state of microbiota in the oral cavity. In this study, we investigated the effect of inactivated Lacticaseibacillus paracasei Probio-01 on plaque-induced gingivitis and the dental plaque microbiota. A total of 32 healthy gingival participants (Group N, using blank toothpaste for 3 months) and 60 patients with plaque-induced gingivitis (30 in Group F, using inactivated Probio-01 toothpaste for 3 months, and 30 in Group B, using blank toothpaste for 3 months, respectively) were recruited. Clinical indices, which included bleeding on probing (BOP), gingival index (GI), and plaque index (PI), were used to assess the severity of gingivitis. Furthermore, 16SrDNA amplicon sequencing was used to explore changes in the gingival state and dental plaque microbiota in patients with plaque-induced gingivitis. The results showed that inactivated Probio-01 significantly reduced clinical indices of gingivitis, including BOP, GI, and PI, in participants with plaque-induced gingivitis and effectively relieved gingival inflammation, compared with that observed in the control group (group B). Inactivated Probio-01 did not significantly influence the diversity of dental plaque microbiota, but increased the relative abundance of dental plaque core bacteria, such as Leptotrichia and Fusobacterium (P < 0.05). Strong correlations were observed between the indices and abundance of dental plaque microbiota. Overall, the inactivated Probio-01 significantly reduced the clinical indices of gingivitis and effectively improved gingival inflammation in patients with plaque-induced gingivitis. The activity of inactivated Probio-01 against plaque-induced gingivitis was possibly mediated by its ability to regulate the dental plaque microbiota, as indicated by the close correlation between the plaque microbiota and clinical indices of gingivitis.

Critical Role of Mineral Fe(IV) Formation in Low Hydroxyl Radical Yields during Fe(II)-Bearing Clay Mineral Oxygenation.

In subsurface environments, Fe(II)-bearing clay minerals can serve as crucial electron sources for O2 activation, leading to the sequential production of O2•-, H2O2, and •OH. However, the observed •OH yields are notably low, and the underlying mechanism remains unclear. In this study, we investigated the production of oxidants from oxygenation of reduced Fe-rich nontronite NAu-2 and Fe-poor montmorillonite SWy-3. Our results indicated that the •OH yields are dependent on mineral Fe(II) species, with edge-surface Fe(II) exhibiting significantly lower •OH yields compared to those of interior Fe(II). Evidence from in situ Raman and Mössbauer spectra and chemical probe experiments substantiated the formation of structural Fe(IV). Modeling results elucidate that the pathways of Fe(IV) and •OH formation respectively consume 85.9-97.0 and 14.1-3.0% of electrons for H2O2 decomposition during oxygenation, with the Fe(II)edge/Fe(II)total ratio varying from 10 to 90%. Consequently, these findings provide novel insights into the low •OH yields of different Fe(II)-bearing clay minerals. Since Fe(IV) can selectively degrade contaminants (e.g., phenol), the generation of mineral Fe(IV) and •OH should be taken into consideration carefully when assessing the natural attenuation of contaminants in redox-fluctuating environments.

Challenges of COVID-19 Case Forecasting in the US, 2020-2021.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

Enrichment of prime-edited mammalian cells with surrogate PuroR reporters.

Prime editing is a programmable genetic method that can precisely generate any desired small-scale variations in cells without requiring double-strand breaks and DNA donors. However, higher editing efficiency is greatly desirable for wide practical applications. In this study, we developed a target-specific prime editing reporter (tsPER) and a universal prime editing reporter (UPER) to facilitate rapid selection of desired edited cells through puromycin screening. The modification efficiency of HEK3_i1CTT_d5G in HEK293T cells improved from 36.37 % to 64.84 % with the incorporation of tsPER. The target sequence of interested genes could be custom inserted into a selection cassette in tsPER to establish personalized reporters. The UPER demonstrated PE3 editing efficiency up to 74.49 % on HEK3_i1CTT_d5G and 73.52 % on HEK3_i1His6, achieved through co-selection with an additional pegRNA (puro) to repair the mutant PuroR cassette. Overall, tsPER and UPER robustly improved the efficiency of prime editing. Both of these approaches expand enrichment strategies for genomically modified cells and accelerate the generation of genetically modified models.

Preparation of a Nanosheeted Uranyl-Organic Framework for Enhanced Photocatalytic Oxidation of Toluene.

Preparation of ultrathin metal-organic framework (MOF) nanosheets is an effective way to improve the catalytic efficiency of MOF photocatalysts owing to their superiority in reducing the recombination rate of photogenerated electrons and holes and enhancing charge transfer. Herein, a light-sensitive two-dimensional uranyl-organic framework named HNU-68 was synthesized. Due to its interlayer stacking structure, the corresponding ultrathin nanosheets with a thickness of 4.4 nm (HNU-68-N) can be obtained through ultrasonic exfoliation. HNU-68-N exhibited an enhanced ability to selectively oxidize toluene to benzaldehyde, with the value of turnover frequency being approximately three times higher than that of the bulk HNU-68. This enhancement is attributed to the smaller size and interface resistance of the layered HNU-68-N nanosheets, which facilitate more thorough substrate contact and faster charge transfer, leading to an improvement in the photocatalytic efficiency. This work provides a potential candidate for the application of ultrathin uranyl-based nanosheets.