Spatiotemporal insight into early pregnancy governed by immune-featured stromal cells.

Endometrial decidualization connecting embryo implantation and placentation is transient but essential for successful pregnancy, which, however, is not systematically investigated. Here, we use a scStereo-seq technology to spatially visualize and define the dynamic functional decidual hubs assembled by distinct immune, endothelial, trophoblast, and decidual stromal cells (DSCs) in early pregnant mice. We unravel the DSC transdifferentiation trajectory and surprisingly discover a dual-featured type of immune-featured DSCs (iDSCs). We find that immature DSCs attract immune cells and induce decidual angiogenesis at the mesenchymal-epithelial transition hub during decidualization initiation. iDSCs enable immune cell recruitment and suppression, govern vascularization, and promote cytolysis at immune cell assembling and vascular hubs, respectively, to establish decidual homeostasis at a later stage. Interestingly, dysfunctional and spatially disordered iDSCs cause abnormal accumulation of immune cells in the vascular hub, which disrupts decidual hub specification and eventually leads to pregnancy complications in DBA/2-mated CBA/J mice.

LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis.

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.

Leaves and stolons transcriptomic analysis provide insight into the role of phytochrome F in potato flowering and tuberization.

Photoperiod plays a critical role in controlling the formation of sexual or vegetative reproductive organs in potato. Although StPHYF-silenced plants overcome day-length limitations to tuberize through a systemic effect on tuberigen StSP6A expression in the stolon, the comprehensive regulatory network of StPHYF remains obscure. Therefore, the present study investigated the transcriptomes of StPHYF-silenced plants and observed that, in addition to known components of the photoperiodic tuberization pathway, florigen StSP3D and other flowering-related genes were activated in StPHYF-silenced plants, exhibiting an early flowering response. Additionally, grafting experiments uncovered the long-distance effect of StPHYF silencing on gene expression in the stolon, including the circadian clock components, flowering-associated MADSs, and tuberization-related regulatory genes. Similar to the AtFT-AtAP1 regulatory module in Arabidopsis, the present study established that the AP1-like StMADS1 functions downstream of the tuberigen activation complex (TAC) and that suppressing StMADS1 inhibits tuberization in vitro and delays tuberization in vivo. Moreover, the expression of StSP6A was downregulated in StMADS1-silenced plants, implying the expression of StSP6A may be feedback-regulated by StMADS1. Overall, these results reveal that the regulatory network of StPHYF controls flowering and tuberization and targets the crucial tuberization factor StMADS1 through TAC, thereby providing a better understanding of StPHYF-mediated day-length perception during potato reproduction.

Suppression of the tonoplast sugar transporter, StTST3.1, affects transitory starch turnover and plant growth in potato.

Transitory starch and vacuolar sugars function as highly dynamic pools of instantly accessible metabolites in plant leaf cells. Their metabolic regulation is critical for plant survival. The tonoplast sugar transporters (TSTs), responsible for sugar uptake into vacuoles, regulate cellular sugar partitioning and vacuolar sugar accumulation. However, whether TSTs are involved in leaf transient starch turnover and plant growth is unclear. Here, we found that suppressing StTST3.1 resulted in growth retardation and pale green leaves in potato plants. StTST3.1-silenced plants displayed abnormal chloroplasts and impaired photosynthetic performance. The subcellular localization assay and the oscillation expression patterns revealed that StTST3.1 encoded a tonoplast-localized protein and responded to photoperiod. Moreover, RNA-seq analyses identified that starch synthase (SS2 and SS6) and glucan water, dikinase (GWD), were downregulated in StTST3.1-silenced lines. Correspondingly, the capacity for starch synthesis and degradation was decreased in StTST3.1-silenced lines. Surprisingly, StTST3.1-silenced leaves accumulated exceptionally high levels of maltose but low levels of sucrose and hexose. Additionally, chlorophyll content was reduced in StTST3.1-silenced leaves. Analysis of chlorophyll metabolic pathways found that Non-Yellow Coloring 1 (NYC1)-like (NOL), encoding a chloroplast-localized key enzyme that catalyzes the initial step of chlorophyll b degradation, was upregulated in StTST3.1-silenced leaves. Transient overexpression of StNOL accelerated chlorophyll b degradation in tobacco leaves. Our results indicated that StTST3.1 is involved in transitory starch turnover and chlorophyll metabolism, thereby playing a critical role in normal potato plant growth.

Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China.

We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.

Latent membrane protein 1 and macrophage-derived TNFα synergistically activate and mobilize invadopodia to drive invasion of nasopharyngeal carcinoma.

Invadopodia are actin-rich membrane protrusions that digest the matrix barrier during cancer metastasis. Since the discovery of invadopodia, they have been visualized as localized and dot-like structures in different types of cancer cells on top of a 2D matrix. In this investigation of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), a highly invasive cancer frequently accompanied by neck lymph node and distal organ metastases, we revealed a new form of invadopodium with mobilizing features. Integration of live-cell imaging and molecular assays revealed the interaction of macrophage-released TNFα and EBV-encoded latent membrane protein 1 (LMP1) in co-activating the EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for mobilizing the invadopodia with lateral movements. This phenomenon endows the invadopodia with massive degradative power, visualized as a shift of focal dot-like digestion patterns on a 2D gelatin to a dendrite-like digestion pattern. Notably, single stimulation of either LMP1 or TNFα could only enhance the number of ordinary dot-like invadopodia, suggesting that the EBV infection sensitizes the NPC cells to form mobilizing invadopodia when encountering a TNFα-rich tumor microenvironment. This study unveils the interplay of EBV and stromal components in driving the invasive potential of NPC via unleashing the propulsion of invadopodia in overcoming matrix hurdles. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

MiR129-5p-loaded exosomes suppress seizure-associated neurodegeneration in status epilepticus model mice by inhibiting HMGB1/TLR4-mediated neuroinflammation.

BACKGROUND: Neuroinflammation contributes to both epileptogenesis and the associated neurodegeneration, so regulation of inflammatory signaling is a potential strategy for suppressing epilepsy development and pathological progression. Exosomes are enriched in microRNAs (miRNAs), considered as vital communication tools between cells, which have been proven as potential therapeutic method for neurological disease. Here, we investigated the role of miR129-5p-loaded mesenchymal stem cell (MSC)-derived exosomes in status epilepticus (SE) mice model. METHODS: Mice were divided into four groups: untreated control (CON group), kainic acid (KA)-induced SE groups (KA group), control exosome injection (KA + Exo-con group), miR129-5p-loaded exosome injection (KA + Exo-miR129-5p group). Hippocampal expression levels of miR129-5p, HMGB1, and TLR4 were compared among groups. Nissl and Fluoro-jade B staining were conducted to evaluate neuronal damage. In addition, immunofluorescence staining for IBA-1 and GFAP was performed to assess glial cell activation, and inflammatory factor content was determined by ELISA. Hippocampal neurogenesis was assessed by BrdU staining. RESULTS: The expression of HMGB1 was increased after KA-induced SE and peaking at 48 h, while hippocampal miR129-5p expression decreased in SE mice. Exo-miR129-5p injection reversed KA-induced upregulation of hippocampal HMGB1 and TLR4, alleviated neuronal damage in the hippocampal CA3, reduced IBA-1 + and GFAP + staining intensity, suppressed SE-associated increases in inflammatory factors, and decreased BrdU + cell number in dentate gyrus. CONCLUSIONS: Exosomes loaded with miR129-5p can protect neurons against SE-mediated degeneration by inhibiting the pro-inflammatory HMGB1/TLR4 signaling axis.

Assimilation of phthalate esters in bacteria.

The massive usage of phthalate esters (PAEs) has caused serious pollution. Bacterial degradation is a potential strategy to remove PAE contamination. So far, an increasing number of PAE-degrading strains have been isolated, and the catabolism of PAEs has been extensively studied and reviewed. However, the investigation into the bacterial PAE uptake process has received limited attention and remains preliminary. PAEs can interact spontaneously with compounds like peptidoglycan, lipopolysaccharides, and lipids on the bacterial cell envelope to migrate inside. However, this process compromises the structural integrity of the cells and causes disruptions. Thus, membrane protein-facilitated transport seems to be the main assimilation strategy in bacteria. So far, only an ATP-binding-cassette transporter PatDABC was proven to transport PAEs across the cytomembrane in a Gram-positive bacterium Rhodococcus jostii RHA1. Other cytomembrane proteins like major facilitator superfamily (MFS) proteins and outer membrane proteins in cell walls like FadL family channels, TonB-dependent transporters, and OmpW family proteins were only reported to facilitate the transport of PAEs analogs such as monoaromatic and polyaromatic hydrocarbons. The functions of these proteins in the intracellular transport of PAEs in bacteria await characterization and it is a promising avenue for future research on enhancing bacterial degradation of PAEs. KEY POINTS: • Membrane proteins on the bacterial cell envelope may be PAE transporters. • Most potential transporters need experimental validation.

Molecular Insights into the Accelerated Sprouting of and Apical Dominance Release in Potato Tubers Subjected to Post-Harvest Heat Stress.

Climate change-induced heat stress (HS) increasingly threatens potato (Solanum tuberosum L.) production by impacting tuberization and causing the premature sprouting of tubers grown during the hot season. However, the effects of post-harvest HS on tuber sprouting have yet to be explored. This study aims to investigate the effects of post-harvest HS on tuber sprouting and to explore the underlying transcriptomic changes in apical bud meristems. The results show that post-harvest HS facilitates potato tuber sprouting and negates apical dominance. A meticulous transcriptomic profiling of apical bud meristems unearthed a spectrum of differentially expressed genes (DEGs) activated in response to HS. During the heightened sprouting activity that occurred at 15-18 days of HS, the pathways associated with starch metabolism, photomorphogenesis, and circadian rhythm were predominantly suppressed, while those governing chromosome organization, steroid biosynthesis, and transcription factors were markedly enhanced. The critical DEGs encompassed the enzymes pivotal for starch metabolism, the genes central to gibberellin and brassinosteroid biosynthesis, and influential developmental transcription factors, such as SHORT VEGETATIVE PHASE, ASYMMETRIC LEAVES 1, SHOOT MERISTEMLESS, and MONOPTEROS. These findings suggest that HS orchestrates tuber sprouting through nuanced alterations in gene expression within the meristematic tissues, specifically influencing chromatin organization, hormonal biosynthesis pathways, and the transcription factors presiding over meristem fate determination. The present study provides novel insights into the intricate molecular mechanisms whereby post-harvest HS influences tuber sprouting. The findings have important implications for developing strategies to mitigate HS-induced tuber sprouting in the context of climate change.

Endogenous miRNA and K+ Co-Activated Dynamic Assembly of DNA Coacervates for Intracellular miRNA Imaging and Mitochondrial Intervention.

Intracellular dynamic assembly of DNA structures may be beneficial for the development of multifunctional nanoplatforms for the regulation of cell behaviors, providing new strategies for disease diagnosis and intervention. Herein, we propose the dynamic assembly of DNA coacervates in living cells triggered by miRNA-21 and K+, which can be used for both miRNA imaging and mitochondrial intervention. The rationale is that miRNA-21 can trigger the hybridization chain reaction to generate G-quadruplex precursors, and K+ can mediate the assembly of G-quadruplex-based coacervates, allowing the colorimetric detection of miRNA-21 ranging from 10 pM to 10 µM. Moreover, the as-formed DNA coacervates can specifically target mitochondria in MCF-7 breast cancer cells using the MCF-7 cell membrane as delivery carriers, which further act as an anionic shielding to inhibit communication between mitochondria and environments, with a significant inhibitory effect on ATP production and cellular migration behaviors. This work provides an ideal multifunctional nanoplatform for rationally interfering with cellular metabolism and migration behaviors through the dynamic assembly of DNA coacervates mediated by endogenous molecules, which has a large number of potential applications in the biomedical field, especially theranostics for cancer metastasis.

OTUD1 ameliorates cerebral ischemic injury through inhibiting inflammation by disrupting K63-linked deubiquitination of RIP2.

BACKGROUND: Inflammatory response triggered by innate immunity plays a pivotal element in the progress of ischemic stroke. Receptor-interacting kinase 2 (RIP2) is implicated in maintaining immunity homeostasis and regulating inflammatory response. However, the underlying mechanism of RIP2 in ischemic stroke is still not well understood. Hence, the study investigated the role and the ubiquitination regulatory mechanism of RIP2 in ischemic stroke. METHODS: Focal cerebral ischemia was introduced by middle cerebral artery occlusion (MCAO) in wild-type (WT) and OTUD1-deficient (OTUD1-/-) mice, oxygen glucose deprivation and reoxygenation (OGD/R) models in BV2 cells and primary cultured astrocytes were performed for monitoring of experimental stroke. GSK2983559 (GSK559), a RIP2 inhibitor was intraventricularly administered 30 min before MCAO. Mice brain tissues were collected for TTC staining and histopathology. Protein expression of RIP2, OTUD1, p-NF-κB-p65 and IκBα was determined by western blot. Localization of RIP2 and OTUD1 was examined by immunofluorescence. The change of IL-1ß, IL-6 and TNF-α was detected by ELISA assay and quantitative real-time polymerase chain reaction. Immunoprecipitation and confocal microscopy were used to study the interaction of RIP2 and OTUD1. The activity of NF-κB was examined by dual-luciferase assay. RESULTS: Our results showed upregulated protein levels of RIP2 and OTUD1 in microglia and astrocytes in mice subjected to focal cerebral ischemia. Inhibition of RIP2 by GSK559 ameliorated the cerebral ischemic outcome by repressing the NF-κB activity and the inflammatory response. Mechanistically, OTUD1 interacted with RIP2 and sequentially removed the K63-linked polyubiquitin chains of RIP2, thereby inhibiting NF-κB activation. Furthermore, OTUD1 deficiency exacerbated cerebral ischemic injury in response to inflammation induced by RIP2 ubiquitination. CONCLUSIONS: These findings suggested that RIP2 mediated cerebral ischemic lesion via stimulating inflammatory response, and OTUD1 ameliorated brain injury after ischemia through inhibiting RIP2-induced NF-κB activation by specifically cleaving K63-linked ubiquitination of RIP2.

ScAREB4 promotes potato constitutive and acclimated freezing tolerance associated with enhancing trehalose synthesis and oxidative stress tolerance.

Cold is a major environmental factor that restrains potato production. Abscisic acid (ABA) can enhance freezing tolerance in many plant species, but powerful evidence of the ABA-mediated signalling pathway related to freezing tolerance is still in deficiency. In the present study, cold acclimation capacity of the potato genotypes was enhanced alongside with improved endogenous content of ABA. Further exogenous application of ABA and its inhibitor (NDGA) could enhance and reduce potato freezing tolerance, respectively. Moreover, expression pattern of downstream genes in ABA signalling pathway was analysed and only ScAREB4 was identified with specifically upregulate in S. commersonii (CMM5) after cold and ABA treatments. Transgenic assay with overexpression of ScAREB4 showed that ScAREB4 promoted freezing tolerance. Global transcriptome profiling indicated that overexpression of ScAREB4 induced expression of TPS9 (trehalose-6-phosphate synthase) and GSTU8 (glutathione transferase), in accordance with improved TPS activity, trehalose content, higher GST activity and accumulated dramatically less H2 O2 in the ScAREB4 overexpressed transgenic lines. Taken together, the current results indicate that increased endogenous content of ABA is related to freezing tolerance in potato. Moreover, ScAREB4 functions as a downstream transcription factor of ABA signalling to promote cold tolerance, which is associated with increased trehalose content and antioxidant capacity.

StHAB1, a negative regulatory factor in abscisic acid signaling, plays crucial roles in potato drought tolerance and shoot branching.

Abscisic acid (ABA) is critical in drought tolerance and plant growth. Group A protein type 2C phosphatases (PP2Cs) are negative regulators of ABA signaling and plant adaptation to stress. Knowledge about the functions of potato group A PP2Cs is limited. Here, we report that the potato group A PP2C StHAB1 is broadly expressed in potato plants and strongly induced by ABA and drought. Suppression of StHAB1 enhanced potato ABA sensitivity and drought tolerance, whereas overexpression of the dominant mutant StHAB1G276D compromised ABA sensitivity and drought tolerance. StHAB1 interacts with almost all ABA receptors and the Snf1-Related Kinase OST1. Suppressing StHAB1 and overexpressing StHAB1G276D alter potato growth morphology; notably, overexpression of StHAB1G276D causes excessive shoot branching. RNA-sequencing analyses identified that the auxin efflux carrier genes StPIN3, StPIN5, and StPIN8 were up-regulated in StHAB1G276D-overexpressing axillary buds. Correspondingly, the auxin concentration was reduced in StHAB1G276D-overexpressing axillary buds, consistent with the role of auxin in repressing lateral branch outgrowth. The expression of BRANCHED1s (StBRC1a and StBRC1b) was unchanged in StHAB1G276D-overexpressing axillary buds, suggesting that StHAB1G276D overexpression does not cause axillary bud outgrowth via regulation of BRC1 expression. Our findings demonstrate that StHAB1 is vital in potato drought tolerance and shoot branching.

Obesity induces male mice infertility via oxidative stress, apoptosis, and glycolysis.

In brief: The current declining trend in male fertility parallels the increasing prevalence of obesity worldwide. This paper revealed that the poor in vitro fertilization rates and decreased sperm motility in obese mice due to excessive oxidative stress enhanced apoptosis and impaired glucose metabolism in the testes. Abstract: Obesity is an urgent public health problem in recent decades, linked to reduced reproductive potential, and negatively affects the success of assisted reproduction technology. The aim of this study is to investigate the mechanisms underlying impaired male fertility caused by obesity. Male C57BL/6 mice fed a high-fat diet for 20 weeks served as mouse models with moderate (20% < body fat rate (BFR) < 30%) and severe obesity (BFR > 30%). Our results showed poor in vitro fertilization rates and decreased sperm motility in obese mice. Abnormal testicular structures were identified in male mice with moderate and severe obesity. The expression level of malondialdehyde increased with obesity severity. This finding indicates that oxidative stress plays a role in male infertility caused by obesity, which was further confirmed by the decreased expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase, and glutathione peroxidases. Our study also found that the expression of cleaved caspase-3 and B-cell lymphoma-2 showed an obesity severity-dependent manner indicating that apoptosis is highly correlated with male infertility caused by obesity. Moreover, the expression of glycolysis-related proteins, including glucose transporter 8, lactate dehydrogenase A, monocarboxylate transporter 2 (MCT2), and MCT4, decreased significantly in the testes of obese male mice, suggesting energy supply for spermatogenesis is impaired by obesity. Taken together, our findings provide evidence that obesity impairs male fertility through oxidative stress, apoptosis, and blockage of energy supply in the testes and suggest that male obesity influences fertility through complex and multiple mechanisms.

Genome sequence analysis provides insights into the mode of 2n egg formation in Solanum malmeanum.

KEY MESSAGE: Our genomic investigation confirms the mechanism of 2n eggs formation in S. malmeanum and aid in optimizing the use of wild germplasm. Wild potatoes are a valuable source of agronomic traits. However, substantial reproductive barriers limit gene flow into cultivated species. 2n gametes are instrumental in preventing endosperm abortion caused by genetic imbalances in the endosperm. However, little is known about the molecular mechanisms underlying the formation of 2n gametes. Here, the wild species Solanum malmeanum Bitter (2x, 1EBN, endosperm balance number) was used in inter- and intrapoloid crosses with other Solanum species, with viable seeds being produced only when S. malmeanum was used as the female parent to cross the 2EBN Solanum genus and with the likely involvement of 2n gametes. Subsequently, we substantiated the formation of 2n eggs in S. malmeanum using fluorescence in situ hybridization (FISH) and genomic sequencing technology. Additionally, the transmission rate of maternal heterozygous polymorphism sites was assessed from a genomic perspective to analyze the mode of 2n egg formation in S. malmeanum × S. tuberosum and S. malmeanum × S. chacoense crosses; each cross acquired an average of 31.12% and 22.79% maternal sites, respectively. This confirmed that 2n egg formation in S. malmeanum attributed to second-division restitution (SDR) coupled with the occurrence of exchange events. The high-throughput sequencing technology used in this study has strong advantages over traditional cytological analyses. Furthermore, S. malmeanum, which has a variety of excellent traits not available from present cultivated potato genepool, has received little research attention and has successfully achieved gene flow in cultivated species in the current study. These findings will facilitate the understanding and optimization of wild germplasm utilization in potatoes.

Identification of major quantitative trait loci and candidate genes for seed weight in soybean.

KEY MESSAGE: Four major quantitative trait loci for 100-seed weight were identified in a soybean RIL population under five environments, and the most likely candidate genes underlying these loci were identified. Seed weight is an important target of soybean breeding. However, the genes underlying the major quantitative trait loci (QTL) controlling seed weight remain largely unknown. In this study, a soybean population of 300 recombinant inbred lines (RILs) derived from a cross between PI595843 (PI) and WH was used to map the QTL and identify candidate genes for seed weight. The RIL population was genotyped through whole genome resequencing, and phenotyped for 100-seed weight under five environments. A total of 38 QTL were detected, and four major QTL, each explained at least 10% of the variation in 100-seed weight, were identified. Six candidate genes within these four major QTL regions were identified by analyses of their tissue expression patterns, gene annotations, and differential gene expression levels in soybean seeds during four developmental stages between two parental lines. Further sequence variation analyses revealed a C to T substitution in the first exon of the Glyma.19G143300, resulting in an amino acid change between PI and WH, and thus leading to a different predicted kinase domain, which might affect its protein function. Glyma.19G143300 is highly expressed in soybean seeds and encodes a leucine-rich repeat receptor-like protein kinase (LRR-RLK). Its predicted protein has typical domains of LRR-RLK family, and phylogenetic analyses reveled its similarity with the known LRR-RLK protein XIAO (LOC_Os04g48760), which is involved in controlling seed size. The major QTL and candidate genes identified in this study provide useful information for molecular breeding of new soybean cultivars with desirable seed weight.

Synthetic bacterial consortia enhanced the degradation of mixed priority phthalate ester pollutants.

Dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DOP) are hazardous chemicals listed as priority pollutants that disrupt endocrine systems. According to available reports, these six priority phthalate esters (PAEs) are considered the most polluting; however, no studies have been conducted on the efficient remediation of these PAEs. We therefore designed and constructed a synthetic bacterial consortium capable of the simultaneous and efficient degradation of six priority PAEs in minimal inorganic salt medium (MSM) and soil. The consortium comprised Glutamicibacter sp. ZJUTW, which demonstrates priority for degrading short-chain PAEs; Cupriavidus sp. LH1, which degrades phthalic acid (PA) and protocatechuic acid (PCA), intermediates of the PAE biodegradation process; and Gordonia sp. GZ-YC7, which efficiently degrades long-chain priority PAEs, including DEHP and DOP. In MSM containing the six mixed PAEs (250 mg/L each), the ZJUTW + YC + LH1 consortium completely degraded the four short-chain PAEs within 48 h, and DEHP (100%) and DOP (62.5%) within 72 h. In soil containing the six mixed PAEs (DMP, DEP, BBP, and DOP, 400 mg/kg each; DBP and DEHP, 500 mg/kg, each), the ZJUTW + YC + LH1 consortium completely degraded DMP, DEP, BBP, and DBP within 6 days, and 70.84% of DEHP and 66.24% of DOP within 2 weeks. The consortium efficiently degraded the six mixed PAEs in both MSM and soil. We thus believe that this synthetic microbial consortium is a strong candidate for the bioremediation of environments contaminated with mixed PAE pollutants.

Clinical application and efficacy analysis of partial cystectomy combined with intravesical chemotherapy in muscle-invasive bladder cancer.

OBJECTIVES: Comparing the long-term tumor control results of partial cystectomy(PC)and radical cystectomy(RC)in the treatment of muscle-invasive bladder cancer, and to explore the feasible method of bladder preservation therapy (BPT)in patients with MIBC. METHODS: We retrospectively analyzed the clinical data of 102 patients with muscle-invasive bladder cancer in our hospital between January 2012 and December 2018, of whom 32 cases in the partial cystectomy group and 70 cases in the radical cystectomy group. We performed a comparative analysis of patient general information, perioperative-related indicators and postoperative follow-up data, comparing OS, PFS, and DSS at 1, 2, 3, 4, and 5 years in both groups, and comparing tumour recurrence and metastasis in postoperative patients. RESULTS: All the 102 cases in this study were successfully completed. Partial cystectomy group and Radical cystectomy group median operating time (169.50(130.00 ~ 225.25) min and 420.00(343.75 ~ 483.75) min, p < 0.001), median intraoperative blood loss was (100(50 ~ 100)ml and 400(200 ~ 1000)ml, p < 0.001), median perioperative blood transfusion volume (0(0 ~ 0)ml and 600(150.00 ~ 906.25)ml, p < 0.001), median total hospital stay (18(14.25 ~ 20.00) and 24.5(20.00 ~ 34.25) days, p < 0.001), median preoperative preparation time (7(4.25 ~ 8.00) and 10(8.00 ~ 13.00) days, p < 0.001), median postoperative hospital stay (9(8.00 ~ 13.50) and 14(11.00 ~ 21.25) days, p < 0.001), the incidence of perioperative blood transfusion was (15.6% and 75.7%, p < 0.001), the incidence of surgical complications was(28.1%(9/32) and 50.0%(35/70), p = 0.033), average hospitalization cost ((26435.76 ± 9877.82) yuan and (58464.36 ± 19753.13) yuan, p < 0.001), the differences were statistically significant (p < 0.05). Perioperative mortality (0 vs. 2.9%(2/70), p = 1), and OS at 1, 2, 3, 4, and 5 years after surgery were (80.0%, 59.8%, 56.1%, 51.0%, 44.6% vs. 76.5%, 67.4%, 64.9%, 57.9%, 52.6%, p = 0.524), PFS (68.2%, 64.6%, 60.3%, 54.8%, 54.8% vs. 82.7%, 78.3%, 75.4%, 67.3%, 62.1%, p = 0.259). DSS (89.9%, 72.4%, 68.6%, 68.6%, 62.4% vs. 87.3%, 83.4%, 80.9%, 73.6%, 68.0%, p = 0.424), and the incidence of tumor recurrence or metastasis was (40.0%(12/30) vs. 25.4%(16/63), p = 0.151), the differences were not statistically significant (p > 0.05). CONCLUSION: In patients with limited solitary T2N0M0 and T3N0M0 muscle-invasive bladder cancer, partial cystectomy plus bladder instillations treatment can achieve comparable tumour control to radical cystectomy. However, patients in the PC group have significant advantages in terms of operative time, intraoperative bleeding, intraoperative and postoperative blood transfusion, preoperative preparation time, total hospital stay, postoperative recovery time, operative costs and operative complications. This option may be considered for such patients with a need for bladder preservation.

A retrospective analysis of preemptive pharmacogenomic testing in 22,918 individuals from China.

BACKGROUND: Pharmacogenomics (PGx) examines the influence of genetic variation on drug responses. With more and more Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines published, PGx is gradually shifting from the reactive testing of single gene toward the preemptive testing of multiple genes. But the profile of PGx genes, especially for the intra-country diversity, is not well understood in China. METHODS: We retrospectively collected preemptive PGx testing data of 22,918 participants from 20 provinces of China, analyzed frequencies of alleles, genotypes and phenotypes of pharmacogenes, predicted drug responses for each participant, and performed comparisons between different provinces. RESULTS AND CONCLUSION: After analyzing 15 pharmacogenes from CPIC guidelines of 31 drugs, we found that 99.97% of individuals may have an atypical response to at least one drug; the participants carry actionable genotypes leading to atypical dosage recommendation for a median of eight drugs. Over 99% of the participants were recommended a decreased warfarin dose based on genetic factors. There were 20 drugs with high-risk ratios from 0.18% to 58.25%, in which clopidogrel showed the highest high-risk ratio. In addition, the high-risk ratio of rasburicase in GUANGDONG (risk ratio (RR) = 13.17, 95%CI:4.06-33.22, p < 0.001) and GUANGXI (RR = 23.44, 95%CI:8.83-52.85, p < 0.001) were significantly higher than that in all provinces. Furthermore, the diversity we observed among 20 provinces suggests that preemptive PGx testing in different geographical regions in China may need to pay more attention to specific genes. These results emphasize the importance of preemptive PGx testing and provide essential evidence for promoting clinical implementation in China.

Endoscopic far-lateral supracerebellar infratentorial approach for resection of dumbbell-shaped trigeminal schwannoma: surgical techniques and preliminary results.

BACKGROUND: Trigeminal schwannomas (TSs) are mostly benign tumors. However, dumbbell-shaped TSs are most challenging for surgeons and pose a high surgical risk. OBJECTIVE: We describe the technique of the purely endoscopic far-lateral supracerebellar infratentorial approach (EFL-SCITA) for removing dumbbell-shaped TSs and further discuss the feasibility of this approach and our experience. METHODS: EFL-SCITA was performed for resection of 5 TSs between January 2020 and March 2023. The entire procedure was performed endoscopically with the goal of total tumor resection. During the operation, the tumor was exposed in close proximity and multiple angles under the endoscope, and the peri-tumor nerves were carefully identified and protected, especially the normal trigeminal fiber bundles around the tumor. RESULTS: All the tumors of 5 patients involved the middle and posterior cranial fossa, of which total removal was achieved in 2 patients and near-total removal in 3 patients. The most common preoperative symptoms were relieved after surgery. Two patients had postoperative mild facial paralysis (House-Brackmann grade II), and 1 patient had abducens palsy; both recovered during the follow-up period. Two patients experienced new postoperative facial hypesthesia, and 1 experienced mastication weakness, which did not recover. There was no tumor recurrence or residual tumor growth during the follow-up period in any of the patients. CONCLUSION: EFL-SCITA is a new and effective alternative for the surgical treatment of TSs. For dumbbell-shaped TSs, this approach provides sufficient surgical field exposure and freedom of operation.