A crystallographic view of the molybdenum cofactor

The molybdenum cofactor (Moco) has been found to be associated with a diverse set of redox enzymes and contains a mononuclear molybdenum or tungsten ion co-ordinated by the dithiolene sulfurs of one or two molybdopterin {a pterin [2-amino-4(1H)-pteridinone] derivative} ligands. The remaining co-ordination sites on the metal are occupied by non-protein oxygen or sulfur species and, occasionally, amino acid side chains. The molybdopterin ligand can exhibit oxidation-state-dependent changes in structure and metal co-ordination, and may also interact with other redox groups in the enzyme. These observations suggest that the molybdopterin may participate in the various electron-transfer reactions associated with the catalytic mechanism of Moco containing enzymes

Susceptibility assessment of geological hazard based on XGBoost and cloud model

In the conventional process of geological hazard assessment, issues such as subjectivity in selecting susceptibility factor weights, randomness, and fuzziness in factor grading are prevalent. The application of a single assessment model can only provide qualitative evaluation of geological hazard susceptibility, lacking quantitative analysis. To overcome these challenges, this study employs an enhanced integrated algorithm (XGBoost) and cloud model. Among 189 disaster potential points in Chaoyang City, twelve susceptibility factors including slope, meteorological conditions, vegetation coverage and elevation were selected. The XGBoost classification algorithm was used to determine susceptibility factor weights. The results showed that the algorithm classification achieved high performance with fitting accuracy of 96.5%. On this basis, the cloud model was employed to transform the fuzzy factor grading into a quantitative problem, establishing a susceptibility evaluation index system for geological hazards in Chaoyang City, thereby assessing their susceptibility. To validate the evaluation index system, the Dadongshan landslide in Chaoyang City was selected as the assessment unit. Results indicate a high susceptibility level for this evaluation unit, consistent with actual conditions. The methodology proposed in this study is promising and can offers reference for evaluating geological hazard susceptibility

A Deep Study of The Impossible Boomerang Distinguishers: New Construction Theory and Automatic Search Methods

The impossible boomerang attack (IBA) is a combination of the impossible differential attack and boomerang attack, which has demonstrated remarkable power in the security evaluation of AES and other block ciphers. However, this method has not received sufficient attention in the field of symmetric cipher analysis. The only existing search method for impossible boomerang distinguishers (IBD), the core of IBAs, is the $\mathcal{UB}\text{-method}$, but it is considered rather rudimentary given current technological advancements and may result in missed opportunities for effective attacks. Therefore, this paper delves into a comprehensive study on the construction theory and automatic search method of IBDs. Theoretically, we propose 5 IBD constructions aligned with the techniques of arbitrary S-box, boomerang distinguisher, Boomerang Connectivity Table, U/L/EBCT and mixed tables for differential propagation for SPN-network block ciphers, and 2 IBD constructions accompanied by state propagation for block ciphers with any structure. Furthermore, we investigate the relationship among these IBD constructions and demonstrate that the most superior IBD aligns precisely with the original definition. Technically, we develop a general SAT-based automatic search tool for IBDs by introducing optimized search strategies of the composite model method and the mixed model method. This tool not only considers the details of each operation but also takes into account the impact of key schedule in a single-key setting. As applications, we first acquire 59584 4-round 1 active word truncated IBDs for AES-128, and 192 of those IBDs cannot be detected by the $\mathcal{UB} \text{-method}$. For Midori64, we first demonstrate the non-existence of $7$-round $1$ active word truncated IBDs, and obtain $7296$ $6$-round $1$ active word truncated IBDs, which is complementary to the finding that there are no existing $6$-round $1$ active word truncated IDs. For PRESENT-80, we get the first 6-round IBDs which cannot be detected by the $\mathcal{UB}\text{-method}$. Those results indicate that our method outperforms the $\mathcal{UB}\text{-method}$ and offer an advantage over IDs. We believe that our work can bring new insights to symmetric cipher analysis

Crystal Structures of the Transcriptional Repressor RolR Reveals a Novel Recognition Mechanism between Inducer and Regulator

Many members of the TetR family control the transcription of genes involved in multidrug resistance and pathogenicity. RolR (Resorcinol Regulator), the recently reported TetR-type regulator for aromatic catabolism from Corynebacterium glutamicum, distinguishes itself by low sequence similarities and different regulation from the previously known members of the TetR family. Here we report the crystal structures of RolR in its effector-bound (with resorcinol) and aop- forms at 2.5 Å and 3.6 Å, respectively. The structure of resorcinol-RolR complex reveal that the hydrogen-bonded network mediated by the four-residue motif (Asp94- Arg145- Arg148- Asp149) with two water molecules and the hydrophobic interaction via five residues (Phe107, Leu111, Leu114, Leu142, and Phe172) are the key factors for the recognition and binding between the resorcinol and RolR molecules. The center-to-center separation of the recognition helices h3-h3′ is decreased upon effector-binding from 34.9 Å to 30.4 Å. This structural change results in that RolR was unsuitable for DNA binding. Those observations are distinct from that in other TetR members. Structure-based mutagenesis on RolR was carried out and the results confirmed the critical roles of the above mentioned residues for effector-binding specificity and affinity. Similar sequence searches and sequence alignments identified 29 RolR homologues from GenBank, and all the above mentioned residues are highly conserved in the homologues. Based on these structural and other functional investigations, it is proposed that RolR may represent a new subfamily of TetR proteins that are invovled in aromatic degradation and sharing common recognition mode as for RolR

TLR3 Regulated Poly I:C-Induced Neutrophil Extracellular Traps and Acute Lung Injury Partly Through p38 MAP Kinase

Acute lung injury (ALI) is the leading cause of morbidity and mortality in critically ill patients. Neutrophil extracellular traps (NETs) have been well documented in the ALI model of bacterial infection. In the present study, we demonstrated that poly I:C could induce pulmonary NETs. Upon poly I:C intratracheal inoculation, neutrophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly increased. Furthermore, the inflammatory cytokines IL-1β, IL-6, and TNF-α in the lung were also significantly elevated. Neutrophil depletion abolished NETs and decreased both neutrophil infiltration and IL-1β in the lung. As expected, DNase I, an inhibitor of MPO and NADPH, decreased pulmonary inflammation and NETs. Blocking of the poly I:C receptor TLR3 reduced lung inflammation and NETs. The MAPK kinase inhibitor p38 diminished the formation of NETs and restored the expression of the tight junction protein claudin-5 in the mouse lung when challenged with poly I:C. In summary, poly I:C induced the formation of pulmonary NETs and ALI, which may be associated with the activation of p38 MAPK and the decreased expression of claudin-5

Cancer-specific survival after diagnosis in men versus women: A pan-cancer analysis.

Comprehensive understanding of cancer-specific survival differences in gender is critical for cancer prevention and treatment. Based on the Surveillance Epidemiology and End Results database, we included data from the most prevalent cancers (lung, esophageal, liver, pancreatic, stomach, colorectal, kidney, and bladder cancer). Cox proportional hazards regression models were constructed to estimate hazard ratios, simultaneously adjusting for demographic, clinical, and treatment factors. Overall, male patients had a worse cancer-specific survival than female patients. After adjustment for cancer prevalence with 1:1 matching, gender remained a significant factor in cancer-specific survival. Among the included cancer types, female patients showed survival benefit in lung, liver, colorectal, pancreatic, stomach, and esophageal cancer, and male patients showed better survival in bladder cancer. Except for kidney cancer, the gender disparity was consistent between cancer patients with nonmetastatic and metastatic disease. Overall, gender appears to be a significant factor influencing cancer-specific survival, and the prognosis of female patients is better than male patients in most cancers. This work might inspire the development of strategies for gender-specific precision cancer prevention and treatment

Altered Growth Trajectory in Children Born to Mothers with Gestational Diabetes Mellitus and Preeclampsia

Purpose: Gestational diabetes mellitus (GDM) and preeclampsia are leading causes of mortality and morbidity in mothers and children. High childhood body mass index (BMI) is among their myriad of negative outcomes. However, little is known about the trajectory of the child BMI exposed to GDM and co-occurring preeclampsia from early to mid-childhood. This study examined the independent and joint impact of GDM and preeclampsia on childhood BMI trajectory. Methods: A population-based sample of 356 mothers were recruited from OB/GYN clinics in New York. Their children were then followed annually from 18 to 72 months. Maternal GDM and preeclampsia status were obtained from medical records. Child BMI was calculated based on their height and weight at annual visits. Results: Hierarchical Linear Modeling was used to evaluate the trajectories of child BMI exposed to GDM and preeclampsia. BMI trajectory by GDM decreased (t-ratio = -2.24, ��=.45, 95% CI=-.05-.95, p = .07), but the trajectory by preeclampsia increased over time (t-ratio = 3.153, ��=.65, 95%CI=.11-1.18, p = .002). Moreover, there was a significant interaction between the two (t-ratio = -2.24, ��=-1.244, 95%CI=.15-2.33, p = .02), such that the BMI of children born to mothers with both GDM and preeclampsia showed consistent increases over time. Conclusions: GDM and preeclampsia could be used as a marker for childhood obesity risk and the identification of a high-risk group, providing potential early intervention. These findings highlight the importance of managing obstetric complications, as an effective method of child obesity prevention