Activation of secondary metabolite gene clusters in Chaetomium olivaceum via the deletion of a histone deacetylase.

Histone acetylation modifications in filamentous fungi play a crucial role in epigenetic gene regulation and are closely linked to the transcription of secondary metabolite (SM) biosynthetic gene clusters (BGCs). Histone deacetylases (HDACs) play a pivotal role in determining the extent of histone acetylation modifications and act as triggers for the expression activity of target BGCs. The genus Chaetomium is widely recognized as a rich source of novel and bioactive SMs. Deletion of a class I HDAC gene of Chaetomium olivaceum SD-80A, g7489, induces a substantial pleiotropic effect on the expression of SM BGCs. The C. olivaceum SD-80A ∆g7489 strain exhibited significant changes in morphology, sporulation ability, and secondary metabolic profile, resulting in the emergence of new compound peaks. Notably, three polyketides (A1-A3) and one asterriquinone (A4) were isolated from this mutant strain. Furthermore, our study explored the BGCs of A1-A4, confirming the function of two polyketide synthases (PKSs). Collectively, our findings highlight the promising potential of molecular epigenetic approaches for the elucidation of novel active compounds and their biosynthetic elements in Chaetomium species. This finding holds great significance for the exploration and utilization of Chaetomium resources. KEY POINTS: • Deletion of a class I histone deacetylase activated secondary metabolite gene clusters. • Three polyketides and one asterriquinone were isolated from HDAC deleted strain. • Two different PKSs were reported in C. olivaceum SD-80A.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: A prospective cohort study.

BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. ERAS can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay (LOS) after surgery. RESULTS: A total of 245 patients (age of 79.8 ± 3.4 yr) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between non-frail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Characterization of the exopolysaccharide produced by Pediococcus acidilactici S1 and its effect on the gel properties of fat substitute meat mince.

Exopolysaccharide produced by lactic acid bacteria has various functions. In the present study, one anti-oxidant polysaccharide fraction, namely S1-EPS, was extracted and purified from Pediococcus acidilactici S1, and its structure and its potential effect on the gel properties of fat substitute meat mince were investigated. The results showed that S1-EPS, one of homogeneous polysaccharides, was mainly composed of Gal, Glc, and Man in molar ratio of 7.61: 15.25: 77.13 and molecular weight of 46.975 kDa. The backbone of EPS-S1 contained →2,6)-α-D-Manp-(1→，→2)-α-D-Manp-(1→,→3)-α-D-Glcp-(1 → and a small amount of→6)-ß-D-Manp-(1→. The linkages of branches in EPS-S1 were mainly composed of α-D-Manp-(1→ attached to a sugar residue →2,6)-α-D-Manp-(1→O-2 or ß-D-Galp-(1→ attached to a sugar residue →2,6)-α-D-Manp-(1→O-6. Furthermore, as S1-EPS increased, the meat minced gel pores decreased, and the surface became smooth. A remarkable inhibitory effect on the lipid oxidation of meat minced gel was found as S1-EPS concentration increased. Overall, S1-EPS was found to have substantial potential in low-fat meat products by serving as a natural, anti-oxidant, and functional additive.

Cobalt-Catalyzed Domino Transformations via Enantioselective C-H Activation/Nucleophilic [3 + 2] Annulation toward Chiral Bridged Bicycles.

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Gelation behavior and mechanism of low methoxyl pectin in the presence of erythritol and sucrose: The role of co-solutes.

Co-solutes such as sucrose and sugar alcohol play a significant part in low methoxyl pectin (LMP) gelation. To explore their gelation mechanism, we investigated the gelation behavior of LMP in the presence of erythritol and sucrose with Ca2+. Results revealed that the introduction of erythritol and sucrose improved the hardness of the gels, fixed more free water, accelerated the rate of gel structuring, and enhanced the gel strength. FT-IR confirmed the reinforced hydrogen bonding and hydrophobic forces between the pectin chains after introducing co-solutes. And it could be observed clearly by SEM that the cross-linking density gel network enhanced with co-solutes. Furthermore, gel disruption experiments suggested the presence of ionic interaction, hydrogen bonding, and hydrophobic forces in LMP gels. Finally, we concluded that the egg-box regions cross-linked only by LMP and Ca2+ were too weak to form a stable gel network structure. Adding co-solutes could increase the amount of cross-linking between pectin chains and enlarge the cross-linking zones, which favored the formation of a dense gel network by more hydrogen bonding and hydrophobic forces. Sucrose gels had superior physicochemical properties and microstructure than erythritol gels due to excellent hydration capacity and chemical structure characteristics.

Molecular Structures, Dipole Moments, and Electronic Properties of ß-HMX under External Electric Field from First-Principles Calculations.

In order to investigate the impact of an external electric field on the sensitivity of ß-HMX explosives, we employ first-principles calculations to determine the molecular structure, dipole moment, and electronic properties of both ß-HMX crystals and individual ß-HMX molecules under varying electric fields. When the external electric field is increasing along the [100], [010], and [001] crystallographic directions of ß-HMX, the calculation results indicate that an increase in the bond length (N1-N3/N1'-N3') of the triggering bond, an increase in the main Qnitro (N3, N3') value, an increase in the minimum surface electrostatic potential, and a decrease in band gap all contribute to a reduction in its stability. Among these directions, the [010] direction exhibits the highest sensitivity, which can be attributed to the significantly smaller effective mass along the [010] direction compared with the [001] and [100] directions. Moreover, the application of an external electric field along the Y direction of the coordinate system on individual ß-HMX molecules reveals that the strong polarization effect induced by the electric field enhances the decomposition of the N1-N3 bonds. In addition, due to the periodic potential energy of ß-HXM crystal, the polarization effect of ß-HMX crystal caused by an external electric field is much smaller than that of a single ß-HXM molecule.

Ultrahigh energy storage in high-entropy ceramic capacitors with polymorphic relaxor phase.

Ultrahigh-power-density multilayer ceramic capacitors (MLCCs) are critical components in electrical and electronic systems. However, the realization of a high energy density combined with a high efficiency is a major challenge for practical applications. We propose a high-entropy design in barium titanate (BaTiO3)-based lead-free MLCCs with polymorphic relaxor phase. This strategy effectively minimizes hysteresis loss by lowering the domain-switching barriers and enhances the breakdown strength by the high atomic disorder with lattice distortion and grain refining. Benefiting from the synergistic effects, we achieved a high energy density of 20.8 joules per cubic centimeter with an ultrahigh efficiency of 97.5% in the MLCCs. This approach should be universally applicable to designing high-performance dielectrics for energy storage and other related functionalities.

The calculated electronic and optical properties of ß-Ga2O3 based on the first principles.

INTRODUCTION: The electronic and optical properties of ß-Ga2O3 have been investigated by CASTEP using first principles. It is found that ß-Ga2O3 has an indirect band gap and the conduction band base is located at the Γ point. The stability of ß-Ga2O3 is demonstrated by the calculation of elastic constants, and the ductility of ß-Ga2O3 is demonstrated by the ratio of Poisson's ratio to shear modulus. The optical property analysis shows that ß-Ga2O3 has a high absorption capacity in the ultraviolet region, but a low absorption capacity in visible and infrared light. CONTEXT: The structure, optical, and electronic properties of ß-Ga2O3 are calculated and analyzed based on first-principles calculation. The optimized structures of ß-Ga2O3 are in good agreement with previously studied. In this paper, the elastic, electronic, and optical properties of ß-Ga2O3 are calculated. METHODS: The CASTEP code was employed to execute these calculations in the present work, where the exchange-correlation interactions were treated in the generalized gradient approximation (GGA) using the Perdew-Burke-Ernzerhof (PBE) functional in the geometry optimizations and electronic and elastic properties.

Surface atom knockout for the active site exposure of alloy catalyst.

The fine regulation of catalysts by the atomic-level removal of inactive atoms can promote the active site exposure for performance enhancement, whereas suffering from the difficulty in controllably removing atoms using current micro/nano-scale material fabrication technologies. Here, we developed a surface atom knockout method to promote the active site exposure in an alloy catalyst. Taking Cu3Pd alloy as an example, it refers to assemble a battery using Cu3Pd and Zn as cathode and anode, the charge process of which proceeds at about 1.1 V, equal to the theoretical potential difference between Cu2+/Cu and Zn2+/Zn, suggesting the electricity-driven dissolution of Cu atoms. The precise knockout of Cu atoms is confirmed by the linear relationship between the amount of the removed Cu atoms and the battery cumulative specific capacity, which is attributed to the inherent atom-electron-capacity correspondence. We observed the surface atom knockout process at different stages and studied the evolution of the chemical environment. The alloy catalyst achieves a higher current density for oxygen reduction reaction compared to the original alloy and Pt/C. This work provides an atomic fabrication method for material synthesis and regulation toward the wide applications in catalysis, energy, and others.

The Clinical Application of Double Taylor Spatial Frame in Segmental Tibial Fracture.

OBJECTIVES: Multi-planar external fixation has been used for the management of segmental tibial fractures with severe soft tissue injuries. However, fewer specialized studies have been reported. The primary aim of this study was to describe our experience of treating fractures of this type using the Taylor Spatial Frame and Ilizarov external fixation methods. METHODS: We retrospectively analyzed 33 patients with segmental tibial fracture treated at our institution between January 2016 and December 2020. The patients were divided into double Taylor Spatial Frame (D-TSF) and Ilizarov groups based on the external fixation structure. Baseline demographic data included sex, age, injury side and cause, open or closed fracture, time from injury to surgery, complications, and external frame removal and fracture healing time. The hip-knee-ankle angle (HKA) was measured from preoperative, immediate postoperative, and final follow-up full-length X-rays of bilateral lower limbs. We determined the degree of deviation in the HKA by calculating the difference between the measured angle and the ideal value of 180°; the absolute value was used to assess recovery of the lower limb force line. At the final follow-up, Johner-Wruhs tibial fracture outcome criteria (J-W TFOC) were used to classify the postoperative function of the affected limb as excellent, good, moderate, or poor. Count data were analyzed with the chi-square test or Fisher's exact test; the Mann-Whitney U test was used for rank data. RESULTS: No statistically significant differences were observed between the two groups in terms of sex, age, side of injury, cause of injury, closed or open fracture, or time between injury and surgery, which indicates that the groups were comparable (p > 0.05). A statistically significant difference was observed in external frame removal and fracture healing time between the D-TSF and Ilizarov groups (36.24 ± 8.34 vs 45.42 ± 10.21 weeks, p = 0.009; 33.33 ± 8.21 vs 42.00 ± 9.78 weeks, p = 0.011). The Johner-Wruhs criteria were used to assess the function of the affected limb, the D-TSF group performed better in correcting the lower limb force line than the Ilizarov group. A statistically significant difference in terms of excellent ratings was observed between the two groups (18/2/1/0 vs 5/5/1/1, p = 0.010). Postoperative follow-up X-rays demonstrated a significant improvement in the HKA in both groups immediately after surgery and at the final follow-up compared to the angle before surgery. At the final follow-up, a statistically significant difference was observed in the degree of deviation in the HKA between the two groups (1.58° ± 0.84° vs 2.37° ± 1.00°, p = 0.023). CONCLUSION: The D-TSF treatment is associated with minimal secondary damage to soft tissue, a straightforward and minimally invasive procedure, multiplanar stable fracture fixation, and optimization of fracture alignment and lower limb force lines, therefore, it is highly effective therapeutic option for segmental tibial fracture.

A new dressing system for accelerating wound recovery after primary total knee arthroplasty: a feasibility study.

PURPOSE: Currently, postoperative wound infection and poor healing of total knee arthroplasty have been perplexing both doctors and patients. We hereby innovatively invented a new dressing system to reduce the incidence of postoperative wound complications. METHODS: We enrolled 100 patients who received primary unilateral total knee arthroplasty and then applied the new dressing system. The data collected included the number of dressing changes, postoperative hospital stay, Visual Analogue Scale score (VAS), the Knee Society Score (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), ASEPSIS scores, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, dressing cost, the frequency of shower and satisfaction. Subsequently, a statistical analysis of the data was performed. RESULTS: Our findings demonstrated the average number of postoperative dressing changes was 1.09 ± 0.38, and the average postoperative hospital stay was 3.72 ± 0.98 days. The average cost throughout a treatment cycle was 68.97 ± 12.54 US dollars. Collectively, the results of VAS, KSS, and KOOS revealed that the pain and function of patients were continuously improved. The results of the four indexes of the ASEPSIS score were 0, whereas the SBSES score was 3.58 ± 0.52 and 4.69 ± 0.46 at two weeks and one month after the operation, respectively. We observed no wound complications until one month after the operation. Remarkably, the satisfaction rate of the patients was 91.85 ± 4.99% one month after the operation. CONCLUSION: In this study, we invented a new dressing system for surgical wounds after total knee arthroplasty and further confirmed its clinical feasibility and safety. CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2000033814, Registered 13/ June/2020.

Efficacy of Breast-Conserving Surgery Versus Modified Radical Surgery in the Treatment of Early Breast Cancer: A Meta-Analysis.

Objective: The study aims to assess and compare the outcomes of modified radical surgery, preserving the nipple-areola complex, against radical mastectomy in patients with triple-negative breast cancer. Emphasis is placed on the clinical significance of this comparison, including its potential impact on patient outcomes, quality of life, and healthcare resources. Methods: Relevant literature from January 2017 to January 2022 was searched in the following databases: PubMed, Embase, MEDLINE, Science Citation Index, Web of Science, China National Knowledge Internet, CCD, and CSPD with keywords. The electric search yielded 613 relevant articles, including 351 from Pubmed, 187 from Embase, 5 from MEDLINE, 21 from CNKI, 4 from CCD, and 45 from CSPD. After duplicate screening, 185 items were eliminated, leaving 428 articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with RevMan 5.3, and sensitivity analysis, cumulative meta-analysis, and publication bias analysis were also performed. A total of 613 relevant articles were collected from the above databases, among which 428 articles remained after the initial screening and were further screened based on the established inclusion and exclusion criteria. The efficacy of modified radical surgery and breast-conserving surgery in the treatment of early breast cancer was assessed by analyzing outcome indicators, including recurrence rate, distant metastatic rate, and three-year survival rate. The methods section details a systematic approach to data collection and analysis, specifying the databases and time frame for the literature search and the statistical tools used for the meta-analysis. The selection process, from the initial number of articles to the final inclusion based on defined criteria, is transparent, ensuring the study's methodological robustness in evaluating the efficacy of surgeries for early breast cancer. Results: Finally, ten articles were found to match the criteria and included in this study. According to the meta-analysis, there was no statistically significant difference between the breast-conserving therapy (BCT) and modified radical mastectomy (MRM) groups in terms of the recurrence rate (OR = 0.76, 95%CI = 0.39, 1.55, P > .05) and distant metastatic rate (OR = 0.81, 95%CI = 0.46, 1.31, P > .05). Nevertheless, the three-year survival rate was 85.2% in the BCT group and 91.7% in the MRM group; a statistically significant difference was observed in the three-year survival rate (OR = 1.47, 95%CI = 1.01, 2.37, P = .03) between the BCT and MRM groups. Accordingly, breast-conserving surgery and modified radical surgery produced comparable clinical outcomes for the treatment of early breast cancer. Conclusion: In the treatment of early breast cancer, breast-conserving surgery has the advantages of less bleeding, fewer clinical complications, and favorable cosmetic outcomes compared with modified radical surgery. Furthermore, patients with breast-conserving surgery showed comparable recurrence and distant metastatic rates to those with modified radical surgery in postoperative follow-up, which, therefore is a suitable treatment option for the widespread recommendation. The study's findings hold significant clinical relevance, implying that while BCT remains a viable option, MRM may offer a survival advantage. This insight empowers both patients and clinicians in making informed, personalized treatment decisions tailored to individual circumstances.

A Method for Predicting the Melting Temperature of Ionic Compounds.

Predicting the melting temperature of materials has always been a topic of great concern. This article proposes an alternative model for determining the melting temperature of materials based on the main idea of the Lindemann melting criterion combined with the first-principles calculations of density functional theory. To verify the accuracy of the melting model, this article selected typical ionic crystals of MgO and 10 alkali metal halides as the validation objects. The calculation results indicate that the melting temperature of the MgO crystals and I-VII compounds is in good agreement with the experimental results.

Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition.

Chemical discovery efforts commonly target individual protein domains. Many proteins, including the EP300/CBP histone acetyltransferases (HATs), contain several targetable domains. EP300/CBP are critical gene-regulatory targets in cancer, with existing high potency inhibitors of either the catalytic HAT domain or protein-binding bromodomain (BRD). A domain-specific inhibitory approach to multidomain-containing proteins may identify exceptional-responding tumor types, thereby expanding a therapeutic index. Here, we discover that targeting EP300/CBP using the domain-specific inhibitors, A485 (HAT) or CCS1477 (BRD) have different effects in select tumor types. Group 3 medulloblastoma (G3MB) cells are especially sensitive to BRD, compared with HAT inhibition. Structurally, these effects are mediated by the difluorophenyl group in the catalytic core of CCS1477. Mechanistically, bromodomain inhibition causes rapid disruption of genetic dependency networks that are required for G3MB growth. These studies provide a domain-specific structural foundation for drug discovery efforts targeting EP300/CBP and identify a selective role for the EP300/CBP bromodomain in maintaining genetic dependency networks in G3MB.

Study of the relationship between pressure and sensitivity of energetic materials based on first-principles calculation.

CONTEXT: In order to study the relationship between the sensitivity and pressure of energetic materials, six kinds of energetic materials were selected as the research object. The crystal structure, electronic, and phonon properties under hydrostatic pressure of 0 ~ 45 GPa were calculated by first principles. The calculation results show that the lattice parameters and band gap values of these six energetic materials decrease with the increase of pressure. The peak of the density of states decreases and moves to the low energy direction, and the electrons become more active. Meanwhile, the effect of pressure on the sensitivity of the energetic materials is analyzed based on the multi-phonon up-pumping theory. The number of doorway modes and integral of projected phonon density of states under high pressure is calculated. The results show that both of them increase with the increase of pressure. And the smaller the value of the band gap, the larger the number of doorway modes and integral of projected phonon density of states, and the more sensitive the energetic material is. METHODS: All calculations are performed using the Materials Studio software based on density functional theory. The Perdew-Burke-Ernzerhof (PBE) functional of the generalized gradient approximation (GGA) is used to calculate the exchange correlation function, and the Grimme dispersion correction method is used to deal with the weak intermolecular interaction. The structure of the compound was optimized by BFGS algorithm. The linear response is used to calculate the phonon properties of energetic materials. The plane wave cutoff energy was set to 830 eV. The K-point grids of TATB, FOX-7, TNX, RDX, TNT, and HMX were chosen as 2 × 2 × 2, 2 × 2 × 1, 2 × 1 × 1, 1 × 1 × 1, 1 × 2 × 1, and 2 × 1 × 2.

Molecular dynamics simulation of sensitivity of HMX, FOX-7, and TATB crystals.

METHODS: This study used molecular dynamics (MD) to simulate three materials (HMX, FOX-7, and TATB) under the NVT ensemble. Six temperatures (100 K, 200 K, 300 K, 400 K, 500 K, and 600 K) were simulated. In addition, the trigger bond lengths, energy bands, and density of states of three materials were obtained at different temperatures and compared with the calculated results at 0 K. CONTEXT: The results indicate that the trigger bond lengths of the three materials are very close to the experimental values. Overall, the maximum and average bond lengths of the trigger bonds increase with increasing temperature. The band gap value decreases with increasing temperature. The changes in trigger bond length and band gap value are consistent with the experimental fact that sensitivity increases with increasing temperature. And Eg > 1 eV is consistently found within the temperature range of 0-600 K, indicating that all three materials are non-metallic compounds.