Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition.

Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini-swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re-excised at 2 weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6 weeks after initial wounding for analysis via histology, bulk RNA-seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16 mm2noT, 28 mm2+T; p = .007) and thickness (0.246 mm2noT, 0.406 mm2+T; p < .001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (p = .024 and p = .013, respectively) compared to noT swine. Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (p < .05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti-androgen topical therapies may be a promising future area of research.

A Healable Quasi-Solid Polymer Electrolyte with Balanced Toughness and Ionic Conductivity.

Solid polymer electrolytes (SPEs) have garnered extensive attention as potential alternatives to traditional liquid electrolytes, primarily due to their prowess in curbing lithium dendrite formation and preventing electrolyte leaks. The quest for SPEs that are both mechanically robust and exhibit superior ionic conductivity has been vigorous. However, achieving a harmonious balance between these two attributes remains a significant challenge. In this study, we introduce a novel quasi-solid electrolyte, ingeniously crafted from a poly(urethane-urea) network, enriched with lithium salts and plasticizers. This innovative composition not only boasts remarkable toughness but also ensures commendable ionic conductivity. Our post-gelation method yields gel polymer electrolytes that undergo rigorous evaluation, leading to an optimized version that stands out with its exceptional room-temperature ionic conductivity (2.94×10-4 S cm-1) and outstanding toughness (11.9 MJ m-3). Moreover, it demonstrates a broad electrochemical window (4.73 V), remarkable stability across a 600-hour cycle test, a high capacity retention exceeding 80 % after 100 cycles at 0.2 C, and a noteworthy self-healing capability. This quasi-solid polymer electrolyte emerges as a promising contender to replace current liquid electrolyte solutions.

Cloning and expression of Neurospora crassa cellobiohydrolase II in Pichia pastoris.

A major cellobiohydrolase of Neurospora crassa CBH2 was successfully expressed in Pichia pastoris. The maximum Avicelase activity in shake flask among seven transformants which selected on 4.0 g/L G418 plates was 0.61 U/mL. The optimal pH and temperature for Avicelase activity of the recombinant CBH2 were determined to be 4.8 and 60 °C, respectively. The new CBH2 maintained 63.5 % Avicelase activity in the range of pH 4.0-10.4, and 60.2 % Avicelase activity in the range of 30-90 °C. After incubation at 70-90 °C for 1 h, the Avicelase activity retained 60.5 % of its initial activity. The presence of Zn2+, Ca2+ or Cd2+ enhanced the Avicelase activity of the CBH2, of which Cd2+ at 10 mM causing the highest increase. The recombinant CBH2 was used to enhance the Avicel hydrolysis by improving the exo-exo-synergism between CBH2 and CBH1 in N.crassa cellulase. The enzymatic hydrolysis yield was increased by 38.1 % by adding recombinant CBH2 and CBH1, and the yield was increased by 215.4 % when the temperature is raised to 70 °C. This work provided a CBH2 with broader pH range and better heat resistance, which is a potential enzyme candidate in food, textile, pulp and paper industries, and other industrial fields.

Palladium-Catalyzed (4 + 1) Annulation of 4-Vinylbenzodioxinones with Sulfur Ylides: Diastereoselective Synthesis of Dihydrobenzofuran Derivatives.

Palladium-catalyzed (4 + 1) annulation of 4-vinylbenzodioxinones with sulfur ylides has been developed to afford various dihydrobenzofuran derivatives in moderate to high yields with excellent diastereoselectivities. The scale-up reaction and further derivations of the product worked well, demonstrating the application potential of the current reaction in organic synthesis.

Salicylaldehyde-Cobalt(II)-Catalyzed C-H Alkoxylation of Indoles with Secondary Alcohols.

A straight and efficient protocol for the synthesis of hindered indole-ethers via C-H alkoxylation of indoles was developed by a cobalt-catalyzed cross-dehydrogenative coupling reaction with secondary alcohols. The selection of the salicylaldehyde-Co(II) catalyst enables the reaction to proceed under conditions without acid or base addition in the presence of limited alcohols. The protocol has broad substrate scope for both indole and secondary alcohols and exhibits good functional tolerance. The synthetic applications are proven by gram-scale reaction and further diversification of the product. Preliminary mechanistic investigations indicate that the activation of C-H bonds is not the rate-determining step of the reaction.

Electrochemical Synthesis of Selenosulfonates from Diselenides and Sulfonyl Hydrazides.

The electrochemical oxidative radical-radical cross-coupling of sulfonyl hydrazides with diselenides for the synthesis of selenosulfonates was successfully accomplished. The method is applicable to a wide range of aromatic/aliphatic sulfonyl hydrazides and diselenides, providing products in good to excellent yields. Notably, this protocol stands out for its green and sustainable nature, as it does not rely on transition metals and oxidizing agents, and the starting materials are cost-effective and readily available.

Topotactic Conversion of Titanium-Oxo Clusters to a Stable TOC-Based Metal-Organic Framework with the Selective Adsorption of Cationic Dyes.

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti6O6(OiPr)8(TTFTC)(phen)2]2 (1, where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1, in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity (qex) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1.

Silver/Antimony-Base Multifunctional Double Perovskite with H/F Substitution Enhance Properties.

Two-dimensional double perovskites have experienced rapid development due to their outstanding optoelectronic properties and diverse structural characteristics. However, the synthesis of high-performance multifunctional compounds and the regulation of their properties still lack relevant examples. Herein, we synthesized two multifunctional compounds, (C6H14N)4AgSbBr8 (1) and (F2-C6H12N)4AgSbBr8 (2), which exhibit high solid-state phase transition temperature, bistable dielectric constant switching, second harmonic generation (SHG), and bright emission. Through H/F substitution, the transition temperature increases and achieves a smaller band gap attributed to reduced interlayer spacing. Furthermore, we investigated the broad emission mechanism of the compounds through first-principles calculation and variable-temperature fluorescence, confirming the presence of the STE1 emission. Our work provides insight into the further development of multifunctional compounds and chemical modification that enhances compound properties.

Shrimp SIRT4 promotes white spot syndrome virus replication.

In WSSV pathogenesis, the molecular mechanisms and the key host factors that regulate the viral replication and morphogenesis remain unclear. However, like most viruses, WSSV is known to induce metabolic reprogramming in several metabolic pathways including the host glutamine metabolism, and several recent reports have suggested that the sirtuins SIRT3, SIRT4, and SIRT5, which belong to a family of NAD+-dependent deacetylases, play an important role in this regulation. Here we focus on characterizing LvSIRT4 from Litopenaeus vannamei and investigate its role in regulating glutamine dehydrogenase (GDH), an important enzyme that promotes glutaminolysis and viral replication. We found that LvSIRT4 silencing led to significant decreases in both WSSV gene expression and the number of viral genome copies. Conversely, overexpression of LvSIRT4 led to significant increases in the expression of WSSV genes and the WSSV genome copy number. Immunostaining in Sf9 insect cells confirmed the presence of LvSIRT4 in the mitochondria and the co-localization of LvSIRT4 and LvGDH in the same cellular locations. In vivo gene silencing of LvSIRT4 significantly reduced the gene expression of LvGDH whereas LvSIRT4 overexpression had no effect. However, neither silencing nor overexpression had any effect on the protein expression levels of LvGDH. Lastly, although GDH activity in uninfected shrimp was unchanged, the GDH enzyme activity in WSSV-infected shrimp was significantly increased after both LvSIRT4 silencing and overexpression. This suggests that although there may be no direct regulation, LvSIRT4 might still be able to indirectly regulate LvGDH via the mediation of one or more WSSV proteins that have yet to be identified.

High-Temperature Phase Transition with Switchable Dielectric Behavior and Significant Photoluminescence Changes in a Zero-Dimensional Hybrid SbBr6 Perovskite.

In the past decade, metal halide materials have been favored by many researchers because of their excellent physical and chemical properties under thermal, electrical, and light stimuli, such as ferroelectricity, dielectric, nonlinearity, fluorescence, and semiconductors, greatly promoting their application in optoelectronic devices. In this study, we successfully constructed an unleaded organic-inorganic hybrid perovskite crystal: [Cl-C6H4-(CH2)2NH3]3SbBr6 (1), which underwent a high-temperature reversible phase transition near Tp = 368 K. The phase transition behavior of 1 was characterized by differential scanning calorimetry, accompanied by a thermal hysteresis of 6 K. In addition, variable-temperature Raman spectroscopy analysis and PXRD further verified the sensitivity of 1 to temperature and the phase transition from low symmetry to high symmetry. Temperature-dependent dielectric testing shows that 1 can be a sensitive switching dielectric constant switching material. Remarkably, 1 exhibits strong photoluminescence emission with a wavelength of 478 nm and a narrow band gap of 2.7 eV in semiconductors. As the temperature increases and decreases, fluorescence undergoes significant changes, especially near Tc, which further confirms the reversible phase transition of 1. All of these findings provide new avenues for designing and assembling new phase change materials with high Tp and photoluminescence properties.

A diet-wide association study for liver cancer risk: findings from a prospective cohort study in Chinese men.

Dietary factors have been extensively investigated as possible risk factors for liver cancer, but the evidence is inconclusive. Our study systematically assessed the association between 142 foods and nutrients and liver cancer risk in a Chinese population using a diet-wide association study. Based on data from 59,844 men in the Shanghai Men's Health Study (SMHS), we assessed the diet intake by dietary questionnaires. Cox regression was used to quantify the association between each food and nutrient and liver cancer risk. A false discovery rate (FDR) of 0.05 was used to select the foods and nutrients for validation. In the cohort, 431 liver cancer cases were identified during 712,373 person-years of follow-up. Retinol (HR per 1 SD increment = 1.09, 95% CI: 1.03-1.14) was associated with a higher risk of liver cancer, whereas onions (HR per 1 SD increment = 0.67, 95% CI: 0.54-0.84) and manganese (HR per 1 SD increment = 0.85, 95% CI: 0.78-0.94) were inversely associated with liver cancer risk. In the replication analysis, estimates for these foods and nutrients were similar in magnitude and direction. Our findings confirm that retinol, onions and manganese were associated with liver cancer risk, which provides reliable evidence between diet and liver cancer development.

Sex-specific impact of dietary patterns on liver cancer incidence: updated results from two population-based cohort studies in China.

PURPOSE: The associations between dietary patterns and liver cancer risk have received much attention, but evidence among the Chinese population is scarce. This study aims to update the results of two cohort studies and provide the sex-specific associations in the Chinese population. METHODS: This study was based on two cohorts from the Shanghai Men's Health Study (SMHS) and the Shanghai Women's Health Study (SWHS). Diet information was collected by validated food frequency questionnaires. Dietary patterns were derived by factor analysis. Cox regression model was utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) for associations between dietary patterns and liver cancer risk. RESULTS: During median follow-up years of 11.2 (male) and 17.1 (female) years, 427 males and 252 females were identified as incident primary liver cancer cases. In males, vegetable-based dietary pattern was inversely associated with liver cancer (HRQ4-Q1: 0.67, 95%CI 0.51-0.88, Ptrend < 0.001). Interaction analysis indicated that in males lower vegetable-based dietary pattern score and older age/medical history of chronic hepatitis combined increase the hazard of liver cancer more than the sum of them, with a 114% and 1061% higher risk, respectively. In females, the fruit-based dietary pattern was associated with a reduced risk of liver cancer (HRQ4-Q1: 0.63, 95%CI 0.42-0.95, Ptrend = 0.03). In both males and females, null associations were observed between the meat-based dietary pattern and the risk of liver cancer. CONCLUSION: A vegetable-based dietary pattern in males and a fruit-based dietary pattern in females tended to have a protective role on liver cancer risk. This study provided updated information that might be applied to guide public health action for the primary prevention of liver cancer.

Effects of Oxygenation Targets on Mortality in Critically Ill Patients in Intensive Care Units: A Systematic Review and Meta-Analysis.

BACKGROUND: The effects of oxygenation targets (partial pressure of arterial oxygen [Pao2], arterial oxygen saturation [Sao2]/peripheral oxygen saturation [Spo2], or inspiratory oxygen concentration [Fio2] on clinical outcomes in critically ill patients remains controversial. We reviewed the existing literature to assess the effects of lower and higher oxygenation targets on the mortality rates of critically ill intensive care unit (ICU) patients. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched from their dates of inception to December 31, 2022, for randomized controlled trials (RCTs) comparing lower and higher oxygenation targets for critically ill patients ≥18 years of age undergoing mechanical ventilation, nasal cannula, oxygen mask, or high-flow oxygen therapy in the ICU. Data extraction was conducted independently, and RoB 2.0 software was used to evaluate the quality of each RCT. A random-effects model was used for the meta-analysis to calculate the relative risk (RR). We used the I2 statistic as a measure of statistical heterogeneity. Certainty of evidence was assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: We included 12 studies with a total of 7416 patients participating in RCTs. Oxygenation targets were extremely heterogeneous between studies. The meta-analysis found no differences in mortality between lower and higher oxygenation targets for critically ill ICU patients (relative risk [RR], 1.00; 95% confidence interval [CI], 0.93-1.09; moderate certainty). The incidence of serious adverse events (RR, 0.93; 95% CI, 0.85-1.00; high certainty), mechanical ventilation-free days through day 28 (mean difference [MD], -0.05; 95%CI, -1.23 to 1.13; low certainty), the number of patients requiring renal replacement therapy (RRT) (RR, 0.96; 95% CI, 0.84-1.10; low certainty), and ICU length of stay (MD, 1.05; 95% CI, -0.04 to 2.13; very low certainty) also did not differ among patients with lower or higher oxygenation targets. CONCLUSIONS: Critically ill ICU patients ≥18 years of age managed with lower and higher oxygenation targets did not differ in terms of mortality, RRT need, mechanical ventilation-free days through day 28, or ICU length of stay. However, due to considerable heterogeneity between specific targets in individual studies, no conclusion can be drawn regarding the effect of oxygenation targets on ICU outcomes.

Residential mobility and liver cancer risk: findings from a prospective cohort study in Chinese women.

BACKGROUND: Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. METHODS: We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. RESULTS: During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44-1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44-1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. CONCLUSIONS: The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health.

[Shenfu Injection regulates macrophage polarization via TLR4/NF-κB pathway to reduce inflammation in chronic heart failure].

This study aimed to investigate the therapeutic effect of Shenfu Injection on mice with chronic heart failure(CHF) and its effect on macrophage polarization. C57BL/6J mice were randomly assigned to the normal and model groups. The CHF model was established by intraperitoneal injection of isoproterenol(ISO, 7.5 mg·kg~(-1), 28 d). The successful modeling was determined by asses-sing the cardiac function and N-terminal pro-brain natriuretic peptide(NT-proBNP). The modeled mice were randomly divided into the model group, Shenfu Injection group, and TAK-242 group, and were injected intraperitoneally with the corresponding drugs for 15 days. Cardiac function was evaluated using echocardiography. Hematoxylin-eosin(HE) staining was used to detect the pathomorphology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the values of serum NT-proBNP, interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), IL-10, and arginase 1(Arg-1). Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. Quantitative polymerase chain reaction(qPCR) and Western blot were used to detect the changes in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway-related mRNA and protein expressions. Compared with the normal group, mice in the model group had lower values of left ventricular ejection fraction(LVEF) and left ventricular fractional shorte-ning(LVFS), higher values of left ventricular internal diastolic end-diastolic(LVIDd), left ventricular internal diastolic end-systolic(LVIDs), NT-proBNP, TNF-α, and IL-6(P<0.01); the number of macrophages increased in cardiac tissues(P<0.05), and the values of M1-F4/80~+CD86~+ were increased(P<0.01), while the values of M2-F4/80~+CD163~+ decreased(P<0.05); the mRNA and protein expressions of TLR4, myeloid differentiation factor 88(MyD88), IκB kinase α(IKKα), and NF-κB p65 in myocardial tissues were significantly elevated(P<0.05, P<0.01). Compared with the model group, mice in the Shenfu Injection and TAK-242 groups showed elevated LVEF, LVFS, IL-10, and Arg-1 levels, and decreased LVIDd, LVIDs, NT-proBNP, TNF-α, and IL-6 levels(P<0.05, P<0.01); the cardiac F4/80~+CD11b~+(macrophage) and M1-F4/80~+ CD86~+ values were significantly down-regulated, while M2-F4/80~+CD163~+ values were increased(P<0.05, P<0.01); and the mRNA and protein expressions of TLR4, MyD88, IKKα, and NF-κB p65 in myocardial tissues were notably decreased(P<0.05, P<0.01). CHF mice have an imbalance of M1/M2 macrophage polarization, with M1-type macrophages predominating. Shenfu Injection promotes macrophage polarization towards M2, inhibits M1-type macrophage activation, and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.

[Identification and expression analysis of whole gene family of Isatis indigotica 4-coumarate: CoA ligase].

The 4-coumarate: CoA ligase(4CL) is a key enzyme in the upstream pathway of phenylpropanoids such as flavonoids, soluble phenolic esters, lignans, and lignins in plants. In this study, 13 4CL family members of Arabidopsis thaliana were used as reference sequences to identify the 4CL gene family candidate members of Isatis indigotica from the reported I. indigotica genome. Further bioinformatics analysis and analysis of the expression pattern of 4CL genes and the accumulation pattern of flavonoids were carried out. Thirteen 4CL genes were obtained, named Ii4CL1-Ii4CL13, which were distributed on chromosomes 1, 2, 3, 4, and 6. The analysis of the gene structure and conserved structural domains revealed the intron number of I. indigotica 4CL genes was between 1 and 12 and the protein structural domains were highly conserved. Cis-acting element analysis showed that there were multiple response elements in the promoter sequence of I. indigotica 4CL gene family, and jasmonic acid had the largest number of reaction elements. The collinearity analysis showed that there was a close relationship between the 4CL gene family members of I. indigotica and A. thaliana. As revealed by qPCR results, the expression analysis of the 4CL gene family showed that 10 4CL genes had higher expression levels in the aboveground part of I. indigotica. The content assay of flavonoids in different parts of I. indigotica showed that flavonoids were mainly accumulated in the aboveground part of plants. This study provides a basis for further investigating the roles of the 4CL gene family involved in the biosynthesis of flavonoids in I. indigotica.

Design and experiment of Panax notoginseng root orientation transplanting device based on YOLOv5s.

Consistent root orientation is one of the important requirements of Panax notoginseng transplanting agronomy. In this paper, a Panax notoginseng orientation transplanting method based on machine vision technology and negative pressure adsorption principle was proposed. With the cut-main root of Panax notoginseng roots as the detection object, the YOLOv5s was used to establish a root feature detection model. A Panax notoginseng root orientation transplanting device was designed. The orientation control system identifies the root posture according to the detection results and controls the orientation actuator to adjust the root posture. The detection results show that the precision rate of the model was 94.2%, the recall rate was 92.0%, and the average detection precision was 94.9%. The Box-Behnken experiments were performed to investigate the effects of suction plate rotation speed, servo rotation speed and the angle between the camera and the orientation actuator(ACOA) on the orientation qualification rate and root drop rate. Response surface method and objective optimisation algorithm were used to analyse the experimental results. The optimal working parameters were suction plate rotation speed of 5.73 r/min, servo rotation speed of 0.86 r/s and ACOA of 35°. Under this condition, the orientation qualification rate and root drop rate of the actual experiment were 89.87% and 6.57%, respectively, which met the requirements of orientation transplanting for Panax notoginseng roots. The research method of this paper is helpful to solve the problem of orientation transplanting of other root crops.

Probing microscale crystallization phenomena: Transforming waste slags into riches.

Metal smelting and combustion of solid fuels produce significant quantities of waste slag, leading to issues such as land occupation and environmental pollution. Understanding and controlling the microscale crystallization phenomena of these slags during thermal treatment is crucial for transforming waste slags into materials suitable for carbon capture or glass ceramics. Previous research has primarily focused on macroscopic crystallization behaviors, significantly advancing the utilization of waste slags in cement clinker production. However, macroscopic results are inadequate for precisely controlling the microscale crystallization behaviors of waste slags. Here, we employed the single hot thermocouple technique to visually explore crystal growth modes, shapes, sizes, numbers, and translational rates of the crystal growth front in a representative blast furnace slag under various isothermal temperatures. The results revealed that crystals exhibited five modes as the isothermal temperature gradually increased, including equiaxed, equiaxed & columnar, columnar, columnar & planar, and planar. Moreover, the translational rate of the crystal growth front increased from 0.011 µm·s-1 to 43.7 µm·s-1 with an increase in the isothermal temperature. Simultaneously, the number of crystals decreased from around 104 to 100 µm-2. On this basis, correlations between microscale crystallization behaviors and isothermal temperature were established to fill the current gap.

Limitations of homologous recombination status testing and poly (ADP-ribose) polymerase inhibitor treatment in the current management of ovarian cancer.

Homologous recombination (HR) is a highly conserved DNA repair system, in which aberrations can lead to the accumulation of DNA damage and genomic scars known as homologous recombination deficiency (HRD). The identification of mutations in key genes (i.e., BRCA1, and BRCA2 (BRCA)) and the quantification of large-scale structural variants (e.g., loss of heterozygosity) are indicators of the HRD phenotype. HRD is a stable biomarker and remains unchanged during recurrence, but fails to reveal the molecular profile of tumor progression. Moreover, interpretation of the current HRD score lacks comprehensiveness, especially for the HR-proficient group. Poly (ADP-ribose) polymerase (PARP) enzymes play an important role in the repair of DNA single-strand breaks, the blockage of which using PARP inhibitors (PARPi) can generate synthetic lethality in cancer cells with HRD. Although numerous studies have demonstrated that the benefit of PARPi is substantial in ovarian cancer (OC) patients, the efficacy is limited by the development of resistance, and seems to be irrespective of HR and/or BRCA mutation status. Moreover, in addition to improving progression-free survival, long-term benefit as overall survival brought by PARPi for advanced, recurrent and refractory OC patients remains unclear. Therefore, further investigations are needed to uncover the role of HR genes beyond BRCA and their interactions with other oncogenic pathways, to determine the value of HRD in the recurrent setting, and to identify alternative strategies for the precise management of advanced, refractory OC patients.