Deciphering tertiary lymphoid structure heterogeneity reveals prognostic signature and therapeutic potentials for colorectal cancer: a multicenter retrospective cohort study.

BACKGROUND: Tertiary lymphoid structures (TLSs) exert a crucial role in the tumor microenvironment (TME), impacting tumor development, immune escape, and drug resistance. Nonetheless, the heterogeneity of TLSs in colorectal cancer (CRC) and their impact on prognosis and treatment response remain unclear. METHODS: We collected genome, transcriptome, clinicopathological information, and digital pathology images from multiple sources. An unsupervised clustering algorithm was implemented to determine diverse TLS patterns in CRC based on the expression levels of 39 TLS signature genes (TSGs). Comprehensive explorations of heterogeneity encompassing mutation landscape, TME, biological characteristics, response to immunotherapy, and drug resistance were conducted using multi-omics data. TLSscore was then developed to quantitatively assess TLS patterns of individuals for further clinical applicability. RESULTS: Three distinct TLS patterns were identified in CRC. Cluster 1 exhibited upregulation of proliferation-related pathways, high metabolic activity, and intermediate prognosis, while Cluster 2 displayed activation of stromal and carcinogenic pathways and a worse prognosis. Both Cluster 1 and Cluster 2 may potentially benefit from adjuvant chemotherapy. Cluster 3, characterized by the activation of immune regulation and activation pathways, demonstrated a favorable prognosis and enhanced responsiveness to immunotherapy. We subsequently employed a regularization algorithm to construct the TLSscore based on 9 core genes. Patients with lower TLSscore trended to prolonged prognosis and a more prominent presence of TLSs, which may benefit from immunotherapy. Conversely, those with higher TLSscore exhibited increased benefits from adjuvant chemotherapy. CONCLUSIONS: We identified distinct TLS patterns in CRC and characterized their heterogeneity through multi-omics analyses. The TLSscore held promise for guiding clinical decision-making and further advancing the field of personalized medicine in CRC.

Regulate the Solvation Structure and Interface by Nitrate in Phosphate-Based Electrolytes for 4.5 V-Class Ni-Rich Batteries.

Phosphate-based electrolyte propels the advanced battery system with high safety. Unfortunately, restricted by poor electrochemical stability, it is difficult to be compatible with advanced lithium metal anodes and Ni-rich cathodes. To alleviate these issues, the study has developed a phosphate-based localized high-concentration electrolyte with a nitrate-driven solvation structure, and the nitrate-derived N-rich inorganic interface shows excellent performance in stabilizing the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode interface and modulating the lithium deposition morphology on the anode. The results show that the Li|| NCM811 cell has exceptional long-cycle stability of >80% capacity retention after 800 cycles at 4.3 V, 1 C. A more prominent capacity retention rate of 93.3% after 200 cycles can be reached with the high voltage of 4.5 V. While being compatible with the phosphate-based electrolyte with good flame retardancy and the good electrochemical stability of Ni-rich lithium metal battery (LMBs) systems, the present work expands the construction of anion-rich solvation structures, which is expected to promote the development of the high-performance LMBs with safety.

PD-1 inhibitor plus concurrent chemoradiotherapy for high-risk locally advanced cervical cancer.

Aim: The prognosis of high-risk, locally advanced cervical cancer (LACC) remains poor following concurrent chemoradiotherapy (CCRT). We investigated whether the effect of CCRT can be enhanced by programmed cell death protein 1 (PD-1) inhibitor. Methods: A retrospective cohort study was conducted to compare the efficacy and safety of CCRT group (n = 82) and PD-1 inhibitor plus CCRT group (n = 70). Results: Compared with the CCRT group, the PD-1 inhibitor plus CCRT group had significantly higher objective response rate, median progression-free survival, leukopenia and fatigue. The addition of PD-1 inhibitor to CCRT showed a favorable trend in overall survival without statistical significance. Conclusion: PD-1 inhibitor plus CCRT presented a significant survival benefit and a manageable safety profile in high-risk LACC.

[Box: see text].

Localized High-Concentration Sulfone Electrolytes with High-Voltage Stability and Flame Retardancy for Ni-Rich Lithium Metal Batteries.

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes.

[Effect of Low-Dose Recombinant Interleukin-2 Therapy on Immunocyte Subsets in Children with Solid Tumor].

OBJECTIVE: To evaluate the effect of low-dose recombinant interleukin-2 (rIL-2) therapy on immunocyte subsets and its side effects in children with solid tumor. METHODS: A total of 22 children (11 males and 11 females) with solid tumor in our department from December 2012 to November 2017 were selected, with a median age of 9 (3-16) years old when starting IL-2 therapy. ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy, and 17 cases achieved complete remission (CR) and 5 cases achieved partial remission (PR). A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year: 4×105 IU/(m2·d), s.c. for every other day, 3 times per week. The immunocyte subsets were detected every 3 months until the end of treatment, meanwhile, disease condition and therapy-related side effects were followed up. RESULTS: After low-dose rIL-2 therapy in 22 children, the absolute values of CD3+ T cells, CD3-CD56+ natural killer cells, CD3+CD4+ helper T cells (Th) and CD3+CD8+ cytotoxic T cells were up-regulated remarkably, as well as Th/suppressor T cells (all P < 0.05). While, there were no significant differences in absolute value and proportion of CD4+CD25+CD127- Treg cells during therapy. Among the 17 children who achieved CR before rIL-2 therapy, 14 cases continued to maintain CR after therapy, while 3 cases relapsed, and with 2 died after treatment abandonment. The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment. In the early stage of low-dose rIL-2 therapy, 1 child developed skin rashes at the injection sites, and 2 children ran a slight to mild transient fever. Their symptoms disappeared without any organ damage after symptomatic treatment. CONCLUSION: Low-dose rIL-2 therapy has good drug tolerance, and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Interface Engineering of MOF-Derived Co3O4@CNT and CoS2@CNT Anodes with Long Cycle Life and High-Rate Properties in Lithium/Sodium-Ion Batteries.

Metal-organic framework materials can be converted into carbon-based nanoporous materials by pyrolysis, which have a wide range of applications in energy storage. Here, we design special interface engineering to combine the carbon skeleton and nitrogen-doped carbon nanotubes (CNTs) with the transition metal compounds (TMCs) well, which mitigates the bulk effect of the TMCs and improves the conductivity of the electrodes. Zeolitic imidazolate framework-67 is used as a precursor to form a carbon skeleton and a large number of nitrogen-doped CNTs by pyrolysis followed by the in situ formation of Co3O4 and CoS2, and finally, Co3O4@CNTs and CoS2@CNTs are synthesized. The obtained anode electrodes exhibit a long cycle life and high-rate properties. In lithium-ion batteries (LIBs), Co3O4@CNTs have a high capacity of 581 mAh g-1 at a high current of 5 A g-1, and their reversible capacity is still 1037.6 mAh g-1 after 200 cycles at 1 A g-1. In sodium-ion batteries (SIBs), CoS2@CNTs have a capacity of 859.9 mAh g-1 at 0.1 A g-1 and can be retained at 801.2 mAh g-1 after 50 cycles. The unique interface engineering and excellent electrochemical properties make them ideal anode materials for high-rate, long-life LIBs and SIBs.

Influence of tillage methods combined with mulching on soil physical properties and potato yield in dry farming area under different precipitation years.

We conducted a field experiment in the dry farming area in south Ningxia from 2018 to 2021, to explore the influence of tillage methods combined with mulching on soil bulk density, aggregate content, soil water storage and potato yield under different precipitation years. There were four tillage methods (15 cm depth ploughing, and 30 cm, 40 cm and 50 cm depth subsoiling) and three mulching measures (mulching with oat straw, plastic film and no mulching), with the ploughing depth of 15 cm without mulching as control. The results showed the combination of tillage and mulching effectively reduced soil bulk density in 0-60 cm layer after three years of farming compared with that prior to the experiment. Under the same tillage mode, the best effect was achieved in mulching with oat straw under different precipitation years. To be specific, the best effect in 20 cm and 40 cm soil layers was achieved in mulching with oat straw for 30 cm depth subsoiling, in 60 cm soil layer for 15 cm ploughing in wet year, and for 40 cm depth subsoiling in 20 cm, 40 cm and 60 cm soil layers in normal and dry years. In 0-20 cm soil layer, the content of >0.25 mm soil aggregate was the highest for 40 cm depth subsoiling with oat straw mul-ching in all the three years. In 20-40 cm soil layer, the content was the highest for 15 cm depth ploughing with oat straw mulching in wet year, and for 40 cm depth subsoiling with oat straw mulching in normal and dry years. In 40-60 cm soil layer, content was the highest for 15 cm depth ploughing with plastic film mulching, 30 cm depth subsoiling with plastic film mulching, and 30 cm depth subsoiling with oat straw mulching in wet, normal and dry years, which was increased by 18.8%, 27.0%, and 35.8%, respectively, compared with the control. In the key growth stage (from squaring to tuber expansion) of potatoes, soil water storage in 0-100 cm layer was optimal for 30 cm depth subsoiling with oat straw mulching in wet year and for 40 cm depth subsoiling with oat straw mulching in normal and dry years, with an increase of 19.4%, 19.5%, and 23.7%, respectively. Potato yield was the highest for 30 cm depth subsoiling with oat straw mulching in wet year and for 40 cm depth subsoiling in normal and dry years, with an increase of 84.6%, 81.7%, and 106.3%, respectively. The correlation analysis showed that improved soil physical properties played a significant role in increasing potato yield, with the most significant role of soil bulk density and soil water storage at the squaring stage. Potato yield was high at a tillage depth of 34.67-36.03 cm. We concluded that the combination of tillage method and mulching could effectively improve soil physical pro-perties and increase soil water storage in the growth stage of potatoes, thereby significantly increa-sing potato yield. Potato yield in dry farming area could be enhanced through 30 cm depth subsoiling with oat straw mulching in wet years, and 40 cm depth subsoiling with oat straw mulching in normal and dry years.

Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature.

PURPOSE: Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. METHODS: The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group (n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group (n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. RESULTS: In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) µm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) µm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels. CONCLUSIONS: NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.

First Report of Erysiphe astragali Causing Powdery Mildew on Astragalus mongholicus in China.

Astragalus mongholicus Bge. [A. membranaceus Bge. var. mongholicus (Bge.) Hsiao] is a highly valuable perennial medicinal plant mainly distributed in China, whose dry roots are known as Huangqi in traditional Chinese medicine for reinforcing vital energy, strengthening superficial resistance, and promoting tissue regeneration (Lin et al. 2000). A. mongholicus roots of high quality are produced in Northwest and North China. Since July 2021, powdery mildew outbreaks happened annually on the leaves of A. mongholicus in a plantation (123° 56' 40'' E, 47° 22' 20'' N) in Qiqihar city, Heilongjiang Province, China. Disease incidence reached 100% by October (Fig. 1A-C), causing severe impairment of growth. Powdery mildew spots of circular or irregular shapes emerged on upper surface of leaf, resulting in plentiful lesion specks. Dense white hyphae appeared chaotically intertwined. Hyphae were hyaline and highly flexuous, 5.3 - 10.7 µm in diameter (n = 20). Chasmothecia were globose or slightly ovoid-shaped and turned dark brown when matured. Chasmothecia (diameter: 135.2 - 222.9 µm, n = 20) existed abundantly on the diseased leaves in the fields. Conidiophores were 89.0 - 129.9 µm in length (n = 20) and composed of one cylindrical, straight foot cell, followed by two cells and one to three conidia. Conidia were slim ellipsoid-shaped, occasionally ovoid-shaped, measuring 14.6 - 24.7 µm by 6.4 to10.4 µm, length/width ratio was 1.8 - 3.0 (n = 30). Hyphal appressoria were nipple-shaped and appeared in singular, occasionally in pairs. Unbranched germ tube emerged reaching out of the germinating conidia while forming an acute angle with the long axis. Comprehensively, the pathogen exhibited micro-morphology of the genus Erysiphe. For molecular identification, pathogen was carefully scraped off diseased leaves for DNA extraction. We used the DNA samples of three biological replicates for the sequencing of the ITS rDNA fragment (primers by (White et al. 1990). All the samples resulted in an identical ITS sequence (deposited in GenBank as OQ390098.1). It displayed 99.83% identity with OP806835.1 of an E. astragali voucher collected in Iran (Fig. 1D-M, O). Hence, our pathogen was identified as an E. astragali stain. Additionally, we amplified the Mcm7 sequence (using primers by (Ellingham et al. 2019), deposited as OQ397582.1). We propagated 40-day-old A. mongholicus plants via germinating seeds in pot soil and performed pathogenicity tests. Firstly, we incubated detached healthy leaves of propagated plants with severely symptomatic leaves collected from the fields in petri dishes under saturated moisture content and room temperature. Powdery mildew symptoms emerged on each healthy leaf (n = 5) after two weeks. Further, we infected healthy plants (n = 5) by gently pressing and rubbing symptomatic leaves on each healthy leaf, and kept them in a greenhouse (24 ℃, 80% humidity, 16/8-hour light/dark cycle). After a month, symptoms emerged on a number of leaves of each infected plant. We performed micromorphology observation (Fig. 1N-P) and ITS sequencing to confirm that the results fulfilled Koch's postulates. Powdery mildew caused by E. astragali on A. strictus in Tibet (Wang and Jiang 2023) and on A. scaberrimus in Inner Mongolia (Sun et al. 2023) have been reported. Here we report powdery mildew caused by E. astragali on Astragalus mongholicus for the first time. These Astragalus spp. are all acknowledged to have medicinal values in China but their usages are quite different.

Clinical feature and genetic analysis of HMBS gene in Chinese patients with acute intermittent porphyria: a systematic review.

Background: Early detection and diagnosis are important crucial to prevent life-threatening acute attacks in patients with acute intermittent porphyria (AIP). We aim to provide comprehensive data on the clinical and hydroxymethylbilane synthase (HMBS) gene variant characteristics and genotype-phenotype association of Chinese patients with AIP in order to improve clinicians' knowledge of AIP and reduce misdiagnosis and mistaken treatment. Methods: We searched the literature on Chinese patients with AIP in PubMed, Web of Science, Wiley Online Library, ScienceDirect and Chinese literature databases up to August 2023 in our analysis to explore the clinical and HMBS gene variant characteristics of Chinese patients with AIP. Results: A total of 41 original articles associated with Chinese AIP patients were included for analysis: 97 variants were detected in 160 unrelated families, including 35 missense, 29 frameshift, 24 splicing and 9 nonsense variants, with c.517C>T being the most common variant. Clinical data were reported in 77 of 160 patients: Most of them were female (67/77) and the age was 28.8 ± 9.9 years. The most common symptom was abdominal pain (73/77, 94.8%), followed by central nervous system symptoms (45/77, 58.4%). 13.0% (10/77) of patients experienced psychiatric symptoms. Hyponatremia was the most common electrolyte abnormality (42/77). 31 patients received carbohydrate loading therapy, and 30 of them were improved. 6 patients were treated with carbohydrate loading combined with hemin therapy and 5 eventually improved. All variants causing premature stop codons, frameshifts or enzyme activity center may experience more severe clinical phenotypes such as seizures, respiratory paralysis, intracranial hemorrhage disorder or respiratory failure. Conclusion: The most common presenting symptom in Chinese AIP patients was abdominal pain, followed by central nervous system symptoms. The HMBS gene analysis in Chinese AIP patients revealed that the heterogeneity is strong and the most common variant was missense mutation, with c.517C>T being the most common variant. The genotype-phenotype association helps guide clinical diagnosis and treatment. However, the treatment for AIP in China is limited and monolithic, and more attention needs to be paid to the treatment.

Functional insights of three RING-finger peroxins in the life cycle of the insect pathogenic fungus Beauveria bassiana.

Peroxisomes play important roles in fungal physiological processes. The RING-finger complex consists of peroxins Pex2, Pex10, and Pex12 and is essential for recycling of receptors responsible for peroxisomal targeting of matrix proteins. In this study, these three peroxins were functionally characterized in the entomopathogenic fungus Beauveria bassiana (Bb). These three peroxins are associated with peroxisomes, in which BbPex2 interacted with BbPex10 and BbPex12. Ablation of these peroxins did not completely block the peroxisome biogenesis, but abolish peroxisomal targeting of matrix proteins via both PTS1 and PTS2 pathways. Three disruptants displayed different phenotypic defects in growth on nutrients and under stress conditions, but have similar defects in acetyl-CoA biosynthesis, development, and virulence. Strikingly, BbPex10 played a less important role in fungal growth on tested nutrients than other two peroxins; whereas, BbPex2 performed a less important contribution to fungal growth under stresses. This investigation reinforces the peroxisomal roles in the lifecycle of entomopathogenic fungi and highlights the unequal functions of different peroxins in peroxisomal biology.

Direct Seawater Electrolysis: From Catalyst Design to Device Applications.

Direct seawater electrolysis (DSE) for hydrogen production, using earth-abundant seawater as the feedstock and renewable electricity as the driving source, paves a new opportunity for flexible energy conversion/storage and smooths the volatility of renewable energy. Unfortunately, the complex environments of seawater impose significant challenges on the design of DSE catalysts, and the practical performance of many current DSE catalysts remains unsatisfactory on the device level. However, many studies predominantly concentrate on the development of electrocatalysts for DSE without giving due consideration to the specific devices. To mitigate this gap, the most recent progress (mainly published within the year 2020-2023) of DSE electrocatalysts and devices are systematically evaluated. By discussing key bottlenecks, corresponding mitigation strategies, and various device designs and applications, the tremendous challenges in addressing the trade-off among activity, stability, and selectivity for DSE electrocatalysts by a single shot are emphasized. In addition, the rational design of the DSE electrocatalysts needs to align with the specific device configuration, which is more effective than attempting to comprehensively enhance all catalytic parameters. This work, featuring the first review of this kind to consider rational catalyst design in the framework of DSE devices, will facilitate practical DSE development.

Dosimetric parameters and safety analysis of 3D-printing non-coplanar template-assisted interstitial brachytherapy for non-centrally recurrent cervical cancer.

Introduction: The prognosis of patients with non-central recurrent cervical cancer (NRCC) remains poor, and treatment options are limited. We aimed to explore the accuracy and safety of the 3D-printed non-coplanar template (3D-PNCT)-assisted 192Ir interstitial brachytherapy (ISBT) in the treatment of NRCC. Material and methods: A total of 36 patients with NRCC who received 3D-PNCT-guided 192Ir ISBT in the First Affiliated Hospital of Zhengzhou University from January 2021 to July 2022 were included in this study. There were 36 3D-PNCTs that were designed and printed. The prescribed dose was 30-36 Gy, divided into five to six times, once a week. To evaluate whether the actual parameters were consistent with the preoperative design, the dosimetric parameters of pre- and postoperative treatment plans were compared, including dose of 90% high-risk clinical target volume (HR-CTV D90), volume percentage of 100% and 150% prescribed dose V100% and V150%, homogeneity index (HI), conformal index (CI), external index (EI), and dose received by 2 cm3 (D2cm3) of the rectum, colon, bladder, and ileum. The safety parameters including occurrence of bleeding, infection, pain, radiation enteritis, and radiation cystitis within 3 months after operation were recorded. Results: All patients successfully completed the treatment and achieved the goals of the preoperative plan. There was no significant difference in the accuracy (HRCTVD90, V100%, EI, CI, and HI) and safety (D2cm3 of rectum, colon, bladder, and ileum) parameters of the postoperative plan compared with the preoperative plan (all p>0.05). Major side effects included bleeding at the puncture site (13.9%), postoperative pain (8.3%), acute radiation cystitis (13.9%), and radiation enteritis (19.4%). There were no serious perioperative complications and no grade 3-4 acute radiotherapy side effects. Conclusion: 3D-PNCT-assisted 192Ir ISBT can be accurately and safely applied in the treatment of patients with NRCC.

Insights into Brochosome Distribution, Synthesis, and Novel Rapid-Release Mechanism in Maiestas dorsalis (Hemiptera: Cicadellidae).

The leafhopper family Cicadellidae, comprising over 22,000 species, exhibits a unique behavior of anointing their bodies with excretions containing brochosomes. Brochosomes are synthesized in the distal segment of the Malpighian tubules and serve various functions, including hydrophobic protection and defense against pathogens and predators. In this study, we investigated the distribution, synthesis, and release mechanisms of brochosomes in the rice pest leafhopper Maiestas dorsalis. Using SEM and TEM, we observed brochosomes' consistent coverage on the integument throughout the insect's life cycle. Moreover, we identified four distinct developmental stages of brochosome synthesis within the distal segment of the Malpighian tubules, originating from the Golgi region. Most importantly, our research revealed a novel and highly efficient release mechanism involving the fusion of brochosome-containing vesicles, leading to a rapid and substantial release of brochosomes into the tubule lumen after molting. These findings shed light on the intricate processes of brochosome synthesis and release in leafhoppers, offering valuable insights into their functional significance and ecological role in these fascinating insects.

HMBS gene mutations and hydroxymethylbilane synthase activity in acute intermittent porphyria: A systematic review.

BACKGROUND: Acute intermittent porphyria (AIP) is caused by a partial deficiency of hydroxymethylbilane synthase and affects heme biosynthesis. Mutations in the HMBS gene result in HMBS deficiency. AIP is a rare disease, and there been insufficient studies on it. This report describes the molecular epidemiology of HMBS gene defects and hydroxymethylbilane synthase activity levels in classical AIP. METHODS: Databases of PubMed, CNKI, and Wang Fang Database were searched for eligible studies to investigate HMBS gene mutations in peripheral blood samples and HMBS activity in erythrocytes of patients with classical AIP. Relevant studies published up to July 15, 2023, from several databases were independently searched and selected by 2 reviewers. Accuracy data and relevant information were extracted from each eligible study by 2 independent researchers and analyzed using statistical software. RESULTS: After pooling the accuracy data from 232 patients of the 15 eligible studies, 90.5% (210/232) of AIP patients had decreased erythrocyte hydroxymethylbilane synthase activity (<70%), and 96 different mutations were identified in 232 patients, including 33 missense (34.4%), 27 splice (28.1%), 19 deletion (19.8%), 8 nonsense (8.3%), 9 insertion (9.4%) mutations. Residual enzyme activities (%) for different groups of type were expressed using mean and 95% confidence interval (95% CI): missense (51.2, 48.5-53.9), splice (57.5, 52.0-59.1), deletion (54.9, 50.7-59.1), nonsense (52.2, 44.4-60.0), insertion (53.2, 47.4-59.0), group analysis P = .17. Subgroups of missense mutations, domain 1 (50.2, 46.0-54.4), domain 2 (52.8, 49.1-56.4), and domain 3 (49.2, 38.3-60.0), Subgroup analysis, P = .62. CONCLUSION: Different mutation types and mutation positions are not associated with the level of hydroxymethylbilane synthase activity. Erythrocyte hydroxymethylbilane synthase activity is often reduced to half of normal in patients with AIP, and the enzyme activity assay has a high diagnostic value in AIP. AIP is highly molecularly heterogeneous, with missense mutations being the most common, followed by splice mutations. R173W and G111R are high-frequency mutations and have been found in multiple families from different countries.

Distribution, Vertical Transmission, and Cooperative Mechanisms of Obligate Symbiotic Bacteria in the Leafhopper Maiestas dorsalis (Hemiptera, Cicadellidea).

Many insects rely on ancient symbiotic bacterial associations for essential nutrition. Auchenorrhyncha commonly harbor two obligate symbionts: Sulcia (Bacteroidetes) and a proteobacterial partner that supplies essential amino acids lacking in their plant-sap diets. In this study focusing on Maiestas dorsalis, we investigated the distribution and vertical transmission of two obligate symbiotic bacteria, Sulcia and Nasuia, within the leafhopper. Sulcia primarily inhabits the external region of the bacteriome, while Nasuia is restricted to the internal region. Both symbionts progressively infiltrate the ovary through the epithelial plug, ultimately reaching the developing primary oocyte. Furthermore, co-phylogenetic analysis suggests a close correlation between the evolution of Auchenorrhyncha insects and the presence of their obligate symbiotic bacteria. Genomic analysis further unveiled the extreme genome reduction of the obligate symbiotic bacteria, with Sulcia retaining genes involved in basic cellular processes and limited energy synthesis, while Nasuia exhibited further gene loss in replication, transcription, translation, and energy synthesis. However, both symbionts retained the genes for synthesizing the essential amino acids required by the host insect. Our study highlights the coevolutionary dynamics between Sulcia, proteobacterial partners, and their insect hosts, shedding light on the intricate nutritional interactions and evolutionary adaptations in Auchenorrhyncha insects.

In-situ constructing amidoxime groups on metal-free g-C3N4 to enhance chemisorption, light absorption, and carrier separation for efficient photo-assisted uranium(VI) extraction.

The development of inexpensive and efficient semiconductor catalysts for photo-assisted uranium extraction from seawater remains a huge challenge. Herein, we have successfully synthesized amidoxime-rich g-C3N4 (AO-C3N4) by simply amidoximing a cyano-rich precursor for photo-assisted uranium extraction from seawater. The amidoxime groups not only served as the U(VI) binding sites for efficient uranium adsorption, but also significantly improved the visible light absorption capacity and carrier separation efficiency via introducing defect energy level, resulting in the excellent photocatalytic activity for AO-C3N4 towards photo-assisted uranium extraction. In the process of photo-assisted uranium extraction, U(VI) was first adsorbed by the amidoxime groups on the AO-C3N4 and then reduced to U(IV), while (UO2)O2·2H2O and (UO2)O2·4H2O were further formed by the oxidation of U(IV) by superoxide radicals (·O2-). Moreover, the generated reactive oxygen species (ROS) under light endowed AO-C3N4 with outstanding antibacterial properties, preventing the limitation of uranium extraction capacity from marine biofouling.

The relationship between processing speed and remodeling spatial patterns of intrinsic brain activity in the elderly with different sleep duration.

Objective: Brain neuroplasticity in which sleep affects the speed of information processing in the elderly population has not been reported. Therefore, this study was conducted to explore the effects of sleep on information processing speed and its central plasticity mechanism in the elderly. Methods: A total of 50 individuals aged 60 and older were enrolled in this case control study. All subjects were divided into two groups according to the sleep time: short sleep duration (< 360 min) (6 men and 19 women; mean age: 66.96 ± 4.28 years old), and non-short sleep duration (> 360 min) (13 men and 12 women). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. Then, the relationships among clinical features, fMRI and cognitive function were analyzed using general linear model. Results: Short sleep duration group showed significantly increased ALFF value in the bilateral middle frontal gyrus and right insula; significantly increased ReHo value in the left superior parietal gyrus, and decreased ReHo value in the right crebellum; significantly decreased DC value in the left inferior occipital gyrus, left superior parietal gyrus and right cerebellum (p < 0.05, AlphaSim correction). The ALFF value of right insula is significantly associated with symbol digit modalities test (SDMT) score (ß = -0.363, p = 0.033). Conclusion: Short sleep duration and processing speed are significantly associated with remodeling spatial patterns of intrinsic brain activity in the elderly.

Limimaricola litoreus sp. nov., isolated from intertidal sand of the Yellow Sea.

A novel species of the genus Limimaricola, designated ASW11-118T, was isolated from an intertidal sand sample of the Yellow Sea, PR China. Growth of strain ASW11-118T occurred at 10-40 °C (optimum, 28 °C), pH 5.5-8.5 (optimum, pH 7.5) and with 0.5-8.0 % (w/v) NaCl (optimum, 1.5%). Strain ASW11-118T has the highest 16S rRNA gene sequence similarity to Limimaricola cinnabarinus LL-001T (98.8%) and 98.6 % to Limimaricola hongkongensis DSM 17492T. Phylogenetic analysis based on genomic sequences indicated that strain ASW11-118T belongs to the genus Limimaricola. The genome size of strain ASW11-118T was 3.8 Mb and DNA G+C content was 67.8 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain ASW11-118T and other members of the genus Limimaricola were below 86.6 and 31.3 %, respectively. The predominant respiratory quinone was ubiquinone-10. The predominant cellular fatty acid was C18 : 1 ω7c. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and one unknown aminolipid. On the basis of the data presented, strain ASW11-118T is considered to represent a novel species of the genus Limimaricola, for which the name Limimaricola litoreus sp. nov. is proposed. The type strain is ASW11-118T (=MCCC 1K05581T=KCTC 82494T).