Non-linear relationship between the body roundness index and metabolic syndrome: data from National Health and Nutrition Examination Survey (NHANES) 1999-2018.

Obesity is an important characteristic manifestation of metabolic syndrome (MetS), and body roundness index (BRI) is one of the anthropometric indicators associated with obesity. However, studies on the relationship between BRI and MetS risk are limited. We aimed to explore the relationship between baseline BRI and MetS in the USA population. Our study used data from the National Health and Nutrition Examination Survey from 1999 to 2018, ultimately enrolling and analysing 47 303 participants. Data-driven tertiles were used to categorise BRI levels, and multivariate logistic regression models were fitted to investigate the association of BRI with MetS in adults. In addition, receiver operating characteristic curve analysis was used to assess the ability of BRI to predict MetS. The distribution of BRI was different across ethnic groups with a gradual decrease in the proportion of non-Hispanic Whites and other races. In addition, BRI was significantly associated with traditional cardiovascular risk factors. Univariate regression analysis indicated BRI to be a moderate risk factor for MetS, and multivariate logistic regression analysis found that BRI remained an independent risk factor for MetS. After adjusting for confounding variables, a non-linear relationship was found between BRI levels and the prevalence of MetS. More importantly, BRI predicted MetS with the largest AUC among anthropometric measures. In summary, elevated baseline BRI levels are independently associated with the development of MetS, and baseline BRI may assist in identifying patients at risk for MetS, leading to early and optimal treatment to improve their outcomes.

Risk factors for malnutrition in patients with nasopharyngeal carcinoma.

BACKGROUND: Malnutrition is a common complication in patients with nasopharyngeal carcinoma (NPC). However, there are few studies on risk factors for malnutrition in NPC patients. Our aims were to identify the risk factors for malnutrition in NPC patients. METHODS: NPC patients were recruited in this cross-sectional study, and they were divided into well-nourished and malnourished groups according to the Global Leadership Initiative on Malnutrition (GLIM). Potential risk factors were initially screened using univariate analysis (p < 0.1), and the selected ones were analyzed by logistic regression analysis (p < 0.05) to identify the risk factors for malnutrition in NPC patients. RESULTS: In total, 305 NPC patients meeting eligibility criteria were enrolled. Multivariate logistic regression analysis revealed that low body mass index (BMI) (OR = 0.596, 95% CI 0.520-0.683, p < 0.001), the high total radiation dose received (OR = 1.046, 95% CI 1.023-1.069, p < 0.001), appetite loss (OR = 2.839, 95% CI 1.269-6.353, p = 0.011), and low PA (OR = 0.993, 95% CI 0.988-0.998, p = 0.008) were risk factors for malnutrition in NPC patients. CONCLUSIONS: The low BMI, the high total radiation dose received, appetite loss, and low prealbumin were risk factors for malnutrition in NPC patients.

Synergy of surface adsorption and intracellular accumulation for removal of uranium with Stenotrophomonas sp: Performance and mechanisms.

Uranium is well-known to have serious adverse effects on the ecological environment and human health. Bioremediation stands out among many remediation methods owing to its being economically feasible and environmentally friendly. This study reported a great promising strategy for eliminating uranium by Stenotrophomonas sp. CICC 23833 in the aquatic environment. The bacterium demonstrated excellent uranium adsorption capacity (qmax = 392.9 mg/g) because of the synergistic effect of surface adsorption and intracellular accumulation. Further analysis revealed that hydroxyl, carboxyl, phosphate groups and proteins of microorganisms were essential in uranium adsorption. Intracellular accumulation was closely related to cellular activity, and the efficiency of uranium processing by the permeabilized bacterial cells was significantly improved. In response to uranium stress, the bacterium was found to release multiple ions in conjunction with uranium adsorption, which facilitates the maintenance of bacterial life activities and the conversion of uranyl to precipitates. These above results indicated that Stenotrophomonas sp. Had great potential application value for the remediation of uranium.

Cadmium-absorptive Bacillus vietnamensis 151-6 reduces the grain cadmium accumulation in rice (Oryza sativa L.): Potential for cadmium bioremediation.

Microbial bioremediation of heavy metal-polluted soil is a promising technique for reducing heavy metal accumulation in crops. In a previous study, we isolated Bacillus vietnamensis strain 151-6 with a high cadmium (Cd) accumulation ability and low Cd resistance. However, the key gene responsible for the Cd absorption and bioremediation potential of this strain remains unclear. In this study, genes related to Cd absorption in B. vietnamensis 151-6 were overexpressed. A thiol-disulfide oxidoreductase gene (orf4108) and a cytochrome C biogenesis protein gene (orf4109) were found to play major roles in Cd absorption. In addition, the plant growth-promoting (PGP) traits of the strain were detected, which enabled phosphorus and potassium solubilization and indole-3-acetic acid (IAA) production. Bacillus vietnamensis 151-6 was used for the bioremediation of Cd-polluted paddy soil, and its effects on growth and Cd accumulation in rice were explored. The strain increased the panicle number (114.82%) and decreased the Cd content in rice rachises (23.87%) and grains (52.05%) under Cd stress, compared with non-inoculated rice in pot experiments. For field trials, compared with the non-inoculated control, the Cd content of grains inoculated with B. vietnamensis 151-6 was effectively decreased in two cultivars (low Cd-accumulating cultivar: 24.77%; high Cd-accumulating cultivar: 48.85%) of late rice. Bacillus vietnamensis 151-6 encoded key genes that confer the ability to bind Cd and reduce Cd stress in rice. Thus, B. vietnamensis 151-6 exhibits great application potential for Cd bioremediation.

Structural variation of mitochondrial genomes sheds light on evolutionary history of soybeans.

The architecture and genetic diversity of mitogenome (mtDNA) are largely unknown in cultivated soybean (Glycine max), which is domesticated from the wild progenitor, Glycine soja, 5000 years ago. Here, we de novo assembled the mitogenome of the cultivar 'Williams 82' (Wm82_mtDNA) with Illumina PE300 deep sequencing data, and verified it with polymerase chain reaction (PCR) and Southern blot analyses. Wm82_mtDNA maps as two autonomous circular chromosomes (370 871-bp Chr-m1 and 62 661-bp Chr-m2). Its structure is extensively divergent from that of the mono-chromosomal mitogenome reported in the landrace 'Aiganhuang' (AGH_mtDNA). Synteny analysis showed that the structural variations (SVs) between two genomes are mainly attributed to ectopic and illegitimate recombination. Moreover, Wm82_mtDNA and AGH_mtDNA each possess six and four specific regions, which are absent in their counterparts and likely result from differential sequence-loss events. Mitogenome SV was further studied in 39 wild and 182 cultivated soybean accessions distributed world-widely with PCR/Southern analyses or a comparable in silico analysis. The results classified both wild and cultivated soybeans into five cytoplasmic groups, named as GSa-GSe and G1-G5; 'Williams 82' and 'Aiganhuang' belong to G1 and G5, respectively. Notably, except for members in GSe and G5, all accessions carry a bi-chromosomal mitogenome with a common Chr-m2. Phylogenetic analyses based on mtDNA structures and chloroplast gene sequences both inferred that G1-G3, representing >90% of cultigens, likely inherited cytoplasm from the ancestor of domestic soybean, while G4 and G5 likely inherited cytoplasm from wild soybeans carrying GSa- and GSe-like cytoplasm through interspecific hybridization, offering new insights into soybean cultivation history.

Pulmonary tuberculosis associated with immune checkpoint inhibitors: a pharmacovigilance study.

We examined case reports of immune checkpoint inhibitors (ICIs) associated pulmonary tuberculosis (PT) using data from the Food and Drug Administration Adverse Event Reporting System database. Disproportionality analysis was performed by using the reporting OR (ROR) with relevant 95% CI. A total of 74 cases of PT related to ICIs therapy were identified. ICIs were significantly associated with over-reporting frequencies of PT (ROR=3.16, 95% CI: 2.51 to 3.98), while the signal was differed between anti-programmed death-1/ligand-1 and anti-cytotoxic T lymphocyte antigen-4 agents. Most indications were lung cancer (64.9%), the median onset age was 70 years, the median time to onset of PT was 70 days, ICIs were discontinued in most cases (85.2%).

Fine mapping of a major QTL qPA7-1 for low hydrocyanic acid content in sorghum-sudangrass hybrid.

The purpose of this study was to study the genetic mechanism of low hydrocyanic acid (HCN) content. The segregation of HCN content trait in fresh stems and leaves was determined in the sorghum (Sorghum bicolor (L.) Moench)-sudangrass (Sorghum sudanense (Piper) Stapf) hybrid F2 population (N = 1200), also used to detect a quantitative trait locus (QTL) for HCN content. Our hypothesis was that the additive effect of QTL was negative, showing that QTL was associated with low HCN. In the present research, a total of 11 simple sequence repeats (SSR) polymorphic primers were screened, and four SSR markers associated with low HCN content were developed based on the bulked segregant analysis method. A high-resolution genetic linkage group of the previously known qPA7-1 locus of the low HCN trait was constructed by analyzing different populations, families, and recombinants. Then, the QTL qPA7-1 of sorghum-sudangrass hybrid was fine-mapped to a 203.6 kb region between markers SORBI4G4-120 and SORBI4G4-680, and seven candidate genes for low HCN were predicted in this region based on sequence comparison with the sorghum reference genome. According to gene annotation, the candidate genes related to low HCN content may be different from those involved in the known regulation mode of sorghum dhurrin biosynthesis and metabolism.

Identification of 8 Feature Genes Related to Clear Cell Renal Cell Carcinoma Progression Based on Co-Expression Analysis.

BACKGROUND: The aim of the study was to screen biomarkers related to clear cell renal cell carcinoma (ccRCC) progression and prognosis. METHODS: 1,026 ccRCC-related genes were dug from 494 ccRCC samples in TCGA based on weighted gene co-expression network analysis, and 7 modules were identified. Afterward, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted on modules of interest. Genes in these modules were taken as the input to construct a protein-protein interaction network. Thereafter, 30 genes with the highest connectivity were taken as core genes. Univariate Cox regression, LASSO Cox regression, and multivariate Cox regression analyses were performed on core genes. Univariate and multivariate Cox regression analyses were performed on patients' clinical characteristics and risk scores. RESULTS: Stage displayed significantly strong correlations with green module and red module (p < 0.001). Genes in modules participated in biological functions including T-cell proliferation and regulation of lymphocyte activation. GSEA showed that high- and low-risk groups exhibited significant enrichment differences in pathways related to immunity, cell migration, and invasion. Immune infiltration analysis also presented a strong correlation between the expression of these 8 genes and immune cell infiltration in ccRCC samples. It was displayed that risk score could be an independent factor to assess patients' prognosis. CONCLUSION: We determined biomarkers relevant to ccRCC progression, offering candidate targets for ccRCC treatment.

Ileus in patients treated with immune checkpoint inhibitors: A retrospective, pharmacovigilance study using Food and Drug Administration Adverse Event Reporting System database.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have been widely used in cancer treatment; however, some case reports suggested that ICIs treatment might result in ileus. This study aims to comprehensively reveal the relationship between ileus and ICIs treatment in real-world cases from Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). METHODS: Reports from January 1, 2011 to December 31, 2020 were extracted from the FAERS. ICIs-related adverse events in patients were defined as related to use of anti-programmed cell death protein 1 antibodies (PD-1, nivolumab and pembrolizumab), anti-programmed cell death-ligand 1 inhibitors (PD-L1, atezolizumab, durvalumab, avelumab, and cemiplimab), and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, ipilimumab and tremelimumab). ICIs-related ileus cases were identified to characterize their clinical features. Reporting odds ratios (ROR) and information component (IC) were used to assess the relationship between ICIs and ileus. RESULTS: Among the 105 001 cases related to ICIs, 245 were reported with ICI-related ileus. The affected patients were mainly elderly (median age, 64.5 years) and male (58%, n = 143). The median onset for all cases was 36 (range 0-880) days, and no statistical difference was observed between monotherapy and combination therapy (PD-1 or PD-L1 plus CTLA-4) (p = 0.21). Most patients required drug withdrawal treatment (n = 113, 74%) and can achieve a recovered-resolved state (n = 72, 46%). All ICIs were significantly associated with ileus (ROR = 4.27, 95%Cl: 3.75-4.85; IC = 2.04, 95%Cl: 1.79-2.31). Ileus events were most commonly reported in PD-1 treatment (n = 164, ROR = 3.83, 95%Cl: 3.28-4.48; IC = 1.90, 95%Cl: 1.62-2.21). CONCLUSION: This pharmacovigilance database analysis suggested that ICIs are related to ileus. However, combination therapy may not speed up the onset of ileus.

MEIOK21: a new component of meiotic recombination bridges required for spermatogenesis.

Repair of DNA double-strand breaks (DSBs) with homologous chromosomes is a hallmark of meiosis that is mediated by recombination 'bridges' between homolog axes. This process requires cooperation of DMC1 and RAD51 to promote homology search and strand exchange. The mechanism(s) regulating DMC1/RAD51-ssDNA nucleoprotein filament and the components of 'bridges' remain to be investigated. Here we show that MEIOK21 is a newly identified component of meiotic recombination bridges and is required for efficient formation of DMC1/RAD51 foci. MEIOK21 dynamically localizes on chromosomes from on-axis foci to 'hanging foci', then to 'bridges', and finally to 'fused foci' between homolog axes. Its chromosome localization depends on DSBs. Knockout of Meiok21 decreases the numbers of HSF2BP and DMC1/RAD51 foci, disrupting DSB repair, synapsis and crossover recombination and finally causing male infertility. Therefore, MEIOK21 is a novel recombination factor and probably mediates DMC1/RAD51 recruitment to ssDNA or their stability on chromosomes through physical interaction with HSF2BP.

1-Nitropyrene exposure induces mitochondria dysfunction and impairs oocyte maturation in mice.

Oocyte quality is essential for a successful pregnancy. 1-Nitropyrene (1-NP) is a widely distributed pollutant in the environment and is well-known for its mutagenicity and carcinogenicity. However, whether 1-NP has toxic effects on mammalian oocyte quality remains unknown. In the present study, we focused on the effect of 1-NP on oocyte maturation using mouse oocytes as an in vitro model. Our study showed that 1-NP exposure disrupted the meiotic spindle assembly and caused chromosome misalignment, further impaired first polar body extrusion, and significantly decreased the fertilization capability in mouse oocytes. Further investigation showed that the mitochondrial membrane potential (MMP) and ATP levels were decreased, and the expression of genes encoding components of the mitochondrial respiratory chain was inhibited in 1-NP exposed oocytes. Meanwhile, 1-NP exposure increased the levels of reactive oxygen species (ROS), inhibited the expression of genes encoding antioxidant enzymes, and increased the frequency of early apoptotic oocytes. Overall, our data suggest that 1-NP exposure disrupts mitochondrial function and intracellular redox balance, ultimately impairing oocyte maturation. These findings reveal the adverse effect of 1-NP exposure on oocyte quality.

The immunophilin CYCLOPHILIN28 affects PSII-LHCII supercomplex assembly and accumulation in Arabidopsis thaliana.

In plant chloroplasts, photosystem II (PSII) complexes, together with light-harvesting complex II (LHCII), form various PSII-LHCII supercomplexes (SCs). This process likely involves immunophilins, but the underlying regulatory mechanisms are unclear. Here, by comparing Arabidopsis thaliana mutants lacking the chloroplast lumen-localized immunophilin CYCLOPHILIN28 (CYP28) to wild-type and transgenic complemented lines, we determined that CYP28 regulates the assembly and accumulation of PSII-LHCII SCs. Compared to the wild type, cyp28 plants showed accelerated leaf growth, earlier flowering time, and enhanced accumulation of high molecular weight PSII-LHCII SCs under normal light conditions. The lack of CYP28 also significantly affected the electron transport rate. Blue native-polyacrylamide gel electrophoresis analysis revealed more Lhcb6 and less Lhcb4 in M-LHCII-Lhcb4-Lhcb6 complexes in cyp28 versus wild-type plants. Peptidyl-prolyl cis/trans isomerase (PPIase) activity assays revealed that CYP28 exhibits weak PPIase activity and that its K113 and E187 residues are critical for this activity. Mutant analysis suggested that CYP28 may regulate PSII-LHCII SC accumulation by altering the configuration of Lhcb6 via its PPIase activity. Furthermore, the Lhcb6-P139 residue is critical for PSII-LHCII SC assembly and accumulation. Therefore, our findings suggest that CYP28 likely regulates PSII-LHCII SC assembly and accumulation by altering the configuration of P139 of Lhcb6 via its PPIase activity.

LIM-Nebulette Reinforces Podocyte Structural Integrity by Linking Actin and Vimentin Filaments.

BACKGROUND: Maintenance of the intricate interdigitating morphology of podocytes is crucial for glomerular filtration. One of the key aspects of specialized podocyte morphology is the segregation and organization of distinct cytoskeletal filaments into different subcellular components, for which the exact mechanisms remain poorly understood. METHODS: Cells from rats, mice, and humans were used to describe the cytoskeletal configuration underlying podocyte structure. Screening the time-dependent proteomic changes in the rat puromycin aminonucleoside-induced nephropathy model correlated the actin-binding protein LIM-nebulette strongly with glomerular function. Single-cell RNA sequencing and immunogold labeling were used to determine Nebl expression specificity in podocytes. Automated high-content imaging, super-resolution microscopy, atomic force microscopy (AFM), live-cell imaging of calcium, and measurement of motility and adhesion dynamics characterized the physiologic role of LIM-nebulette in podocytes. RESULTS: Nebl knockout mice have increased susceptibility to adriamycin-induced nephropathy and display morphologic, cytoskeletal, and focal adhesion abnormalities with altered calcium dynamics, motility, and Rho GTPase activity. LIM-nebulette expression is decreased in diabetic nephropathy and FSGS patients at both the transcript and protein level. In mice, rats, and humans, LIM-nebulette expression is localized to primary, secondary, and tertiary processes of podocytes, where it colocalizes with focal adhesions as well as with vimentin fibers. LIM-nebulette shRNA knockdown in immortalized human podocytes leads to dysregulation of vimentin filament organization and reduced cellular elasticity as measured by AFM indentation. CONCLUSIONS: LIM-nebulette is a multifunctional cytoskeletal protein that is critical in the maintenance of podocyte structural integrity through active reorganization of focal adhesions, the actin cytoskeleton, and intermediate filaments.

Bidirectional relationship between parental psychological control and adolescent maladjustment.

INTRODUCTION: This study explores the longitudinal and bidirectional relations between paternal/maternal psychological control and adolescent maladjustment (i.e., internalizing symptoms, aggression, and association with deviant peers). METHODS: This longitudinal investigation was conducted at two time points over a one-year interval with participants comprising 543 Chinese adolescents aged 10 to 13 (mean age at Time 1 = 11.29; 51.93% girls). The performed measurements encompassed paternal/maternal psychological control, adolescent internalizing symptoms, aggression, association with deviant peers, and demographic information. RESULTS: The findings of a cross-lagged model analysis revealed that paternal psychological control was longitudinally and positively related to adolescent internalizing symptoms and aggression. Maternal psychological control was not significantly related to any domain of adolescent maladjustment. In turn, adolescent association with deviant peers was longitudinally and positively associated with both parents' psychological control. CONCLUSIONS: Parental psychological control was bidirectionally associated with adolescent maladjustment in general, and paternal psychological control played a crucial role on adolescent maladjustment in the Chinese cultural context. The study's findings supported the reciprocal model of parent-child interaction, and extended it by highlighting the apprehension of the characteristics of parental impact from a cultural perspective. The study results add to the current scholarly understanding of parental psychological control in the non-western cultural context.

Extreme In-Plane Thermal Conductivity Anisotropy in Titanium Trisulfide Caused by Heat-Carrying Optical Phonons.

High in-plane anisotropies arise in layered materials with large structural difference along different in-plane directions. We report an extreme case in layered TiS3, which features tightly bonded atomic chains along the b-axis direction, held together by weaker, interchain bonding along the a-axis direction. Experiments show thermal conductivity along the chain twice as high as between the chain, an in-plane anisotropy higher than any other layered materials measured to date. We found that in contrast to most other materials, optical phonons in TiS3 conduct an unusually high portion of heat (up to 66% along the b-axis direction). The large dispersiveness of optical phonons along the chains, contrasted to many fewer dispersive optical phonons perpendicular to the chains, is the primary reason for the observed high anisotropy in thermal conductivity. The finding discovers materials with unusual thermal conduction mechanism, as well as provides new material platforms for potential heat-routing or heat-managing devices.

An operon consisting of a P-type ATPase gene and a transcriptional regulator gene responsible for cadmium resistances in Bacillus vietamensis 151-6 and Bacillus marisflavi 151-25.

BACKGROUND: Cadmium (Cd) is a severely toxic heavy metal to most microorganisms. Many bacteria have developed Cd2+ resistance. RESULTS: In this study, we isolated two different Cd2+ resistance Bacillus sp. strains, Bacillus vietamensis 151-6 and Bacillus marisflavi 151-25, which could be grown in the presence of Cd2+ at concentration up to 0.3 mM and 0.8 mM, respectively. According to the genomic sequencing, transcriptome analysis under cadmium stress, and other related experiments, a gene cluster in plasmid p25 was found to be a major contributor to Cd2+ resistance in B. marisflavi 151-25. The cluster in p25 contained orf4802 and orf4803 which encodes an ATPase transporter and a transcriptional regulator protein, respectively. Although 151-6 has much lower Cd2+ resistance than 151-25, they contained similar gene cluster, but in different locations. A gene cluster on the chromosome containing orf4111, orf4112 and orf4113, which encodes an ATPase transporter, a cadmium efflux system accessory protein and a cadmium resistance protein, respectively, was found to play a major role on the Cd2+ resistance for B. vietamensis 151-6. CONCLUSIONS: This work described cadmium resistance mechanisms in newly isolated Bacillus vietamensis 151-6 and Bacillus marisflavi 151-25. Based on homologies to the cad system (CadA-CadC) in Staphylococcus aureus and analysis of transcriptome under Cd2+ induction, we inferred that the mechanisms of cadmium resistance in B. marisflavi 151-25 was as same as the cad system in S. aureus. Although Bacillus vietamensis 151-6 also had the similar gene cluster to B. marisflavi 151-25 and S. aureus, its transcriptional regulatory mechanism of cadmium resistance was not same. This study explored the cadmium resistance mechanism for B. vietamensis 151-6 and B. marisflavi 151-25 and has expanded our understanding of the biological effects of cadmium.

Identification and characterization of sequence signatures in the Bacillus subtilis promoter Pylb for tuning promoter strength.

OBJECTIVE: To thoroughly characterize the Pylb promoter and identify the elements that affect the promoter activity. RESULT: The sequences flanking the - 35 and - 10 box of the Pylb promoter were divided into six segments, and six random-scanning mutant promoter libraries fused to an enhanced green fluorescent protein EGFP were made and analyzed by flow cytometry. Our results showed that the four nucleotides flanking the - 35 box could mostly influence the promoter activity, and this influence was related to the GC content. The promoters mutated in these regions were successfully used for expressing the gene ophc2 encoding organophosphorus hydrolase (OPHC2) and the gene katA encoding catalase (KatA). CONCLUSION: Our work identified and characterized the sequence signatures of the Pylb promoter that could tune the promoter strength, providing further information for the potential application of this promoter. Meanwhile, the sequence signatures have the potential to be used for tuning gene expression in enzyme production, metabolic engineering, and synthetic biology.

Single-cell transcriptome sequencing reveals that cell division cycle 5-like protein is essential for porcine oocyte maturation.

The brilliant cresyl blue (BCB) test is used in both basic biological research and assisted reproduction to identify oocytes likely to be developmentally competent. However, the underlying molecular mechanism targeted by the BCB test is still unclear. To explore this question, we first confirmed that BCB-positive porcine oocytes had higher rates of meiotic maturation, better rates of cleavage and development into blastocysts, and lower death rates. Subsequent single-cell transcriptome sequencing on porcine germinal vesicle (GV)-stage oocytes identified 155 genes that were significantly differentially expressed between BCB-negative and BCB-positive oocytes. These included genes such as cdc5l, ldha, spata22, rgs2, paip1, wee1b, and hsp27, which are enriched in functionally important signaling pathways including cell cycle regulation, oocyte meiosis, spliceosome formation, and nucleotide excision repair. In BCB-positive GV oocytes that additionally had a lower frequency of DNA double-strand breaks, the CDC5L protein was significantly more abundant. cdc5l/CDC5L inhibition by short interference (si)RNA or antibody microinjection significantly impaired porcine oocyte meiotic maturation and subsequent parthenote development. Taken together, our single-oocyte sequencing data point to a potential new role for CDC5L in porcine oocyte meiosis and early embryo development, and supports further analysis of this protein in the context of the BCB test.

Interplay between n→π* Interactions and Dynamic Covalent Bonds: Quantification and Modulation by Solvent Effects.

Orbital donor-acceptor interactions play critical roles throughout chemistry, and hence, their regulation and functionalization are of great significance. Herein we demonstrate for the first time the investigation of n→π* interactions through the strategy of dynamic covalent chemistry (DCC), and we further showcase its use in the stabilization of imine. The n→π* interaction between donor X and acceptor aldehyde/imine within 2-X-2'-formylbiphenyl derivatives was found to significantly influence the thermodynamics of imine exchange. The orbital interaction was then quantified through imine exchange, the equilibrium of which was successfully correlated with the difference in natural bond orbital stabilization energy of n→π* interactions of aldehyde and its imine. Moreover, the examination of solvent effects provided insights into the distinct feature of the modulation of n→π* interaction with aprotic and protic solvents. The n→π* interaction involving imine was enhanced in protic solvents due to hydrogen bonding with the solvent. This finding further enabled the stabilization of imine in purely aqueous solution. The strategies and results reported should find application in many fields, including molecular recognition, biological labeling, and asymmetric catalysis.

Novel Inhalable Ciprofloxacin Dry Powders for Bronchiectasis Therapy: Mannitol-Silk Fibroin Binary Microparticles with High-Payload and Improved Aerosolized Properties.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease associated with the high morbidity and mortality. Long-term intermittent therapy by inhalable antibiotics has recently emerged as an effective approach for NCFB treatment. However, the effective delivery of antibiotics to the lung requires administering a high dose to the site of infection. Herein, we investigated the novel inhalable silk-based microparticles as a promising approach to deliver high-payload ciprofloxacin (CIP) for NCFB therapy. Silk fibroin (SF) was applied to improve drug-payload and deposit efficiency of the dry powder particles. Mannitol was added as a mucokinetic agent. The dry powder inhaler (DPI) formulations of CIP microparticles were evaluated in vitro in terms of the aerodynamic performance, particle size distribution, drug loading, morphology, and their solid state. The optimal formulation (highest drug loading, 80%) exhibited superior aerosolization performance in terms of fine particle fraction (45.04 ± 0.84%), emitted dose (98.10 ± 1.27%), mass median aerodynamic diameter (3.75 ± 0.03 µm), and geometric standard deviation (1.66 ± 0.10). The improved drug loading was due to the electrostatic interactions between the SF and CIP by adsorption, and the superior aerosolization efficiency would be largely attributed to the fluffy and porous cotton-like property and low-density structure of SF. The presented results indicated the novel inhalable silk-based DPI microparticles of CIP could provide a promising strategy for the treatment of NCFB.