Predicting abiraterone efficacy in advanced prostate cancer: Insights from marker of proliferation Ki67.

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.

The impact of general anesthesia on the outcomes of preterm infants with gestational age less than 32 weeks delivered via cesarean section.

Background: Recent advancements in China's perinatal and neonatal intensive care have significantly reduced neonatal mortality, yet preterm births before 32 weeks remain the primary cause of neonatal fatalities and contribute to long-term disabilities. The prognosis of very preterm infants (VPIs) is significantly affected by factors including the intrauterine environment, delivery method and neonatal intensive care. Cesarean section which often used for preterm births has implications that are not fully understood, particularly concerning the type of anesthesia used. This study examines the impact of general anesthesia (GA) during cesarean delivery on VPI outcomes, aiming to identify strategies for mitigating GA-associated risks. Methods: This cohort study analyzed 1,029 VPIs born via cesarean section under 32 weeks' gestation at our single-center from 1 January 2018, to 31 December 2022. Detailed medical records, encompassing perioperative information, maternal data and neonatal outcomes were meticulously examined. The primary aim of this investigation was to compare maternal characteristics and neonatal outcomes between VPIs delivered under GA and neuraxial anesthesia (NA). A significance level of p < 0.05 was established. Results: Of the 1,029 VPIs analyzed, 87.95% (n = 905) were delivered via NA and 12.05% (n = 124) via GA. Mothers with hypertensive pregnancy diseases and emergency operations were more inclined to choose GA. VPIs delivered under GA showed a lower Apgar score at one and 5 minutes (p < 0.01), increased need for tracheal intubation resuscitation (32.2% vs. 12.2%, p < 0.01) and a greater incidence of severe neurological injury (SNI) (14.5% vs. 5%, p < 0.01). Multivariable analysis revealed GA was significantly associated with lower Apgar scores at one (OR 6.321, 95% CI 3.729-10.714; p < 0.01) and 5 minutes (OR 4.535, 95% CI 2.975-6.913; p < 0.01), higher risk of tracheal intubation resuscitation (OR = 3.133, 95% CI = 1.939-5.061; p < 0.01) and SNI (OR = 3.019, 95% CI = 1.615-5.643; p < 0.01). Furthermore, for VPIs delivered under GA, a prolonged interval from skin incision to fetus delivery was associated with a lower 5-min Apgar score (p < 0.01). Conclusion: This study revealed the significant impact of GA on adverse outcomes among VPIs. In cases when GA is required, proactive measures should be instituted for the care of VPIs such as expediting the interval from skin incision to fetal delivery.

Agreements between GLIM using left calf circumference as criterion for reduced muscle mass and PG-SGA, and GLIM using ASMI for the diagnosis of malnutrition in gastric cancer patients.

OBJECTIVE: this study aimed to explore the agreements between the Global Leadership Initiative on Malnutrition (GLIM) using left calf circumference (CC) as criterion for reduced muscle mass and the Patient-Generated Subjective Global Assessment (PG-SGA), or GLIM using appendicular skeletal muscle index (ASMI) for the diagnosis of malnutrition in gastric cancer patients. METHODS: the Nutritional Risk Screening 2002 (NRS 2002) was used as nutritional risk screening. PG-SGA and GLIM were applied for malnutrition diagnosis. Agreements were evaluated by Kappa, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC). RESULTS: a total of 405 gastric cancer patients were included. The values of Kappa, sensitivity, specificity, PPV, NPV, accuracy and AUC were 0.463, 67.9 %, 87.3 %, 92.9 %, 52.8 %, 73.6 % and 0.776, and 0.496, 76.7 %, 78.0 %, 89.4 %, 57.9 %, 77.0 % and 0.773, respectively, between GLIM using CC with or without NRS 2002 and PG-SGA. All values of agreement were higher than 0.800 or 80.0 % between GLIM using left CC and GLIM using ASMI. CONCLUSION: the agreements were both acceptable between GLIM using left CC and PG-SGA, and GLIM using ASMI. Left calf circumference can be one of the credible references indicating a reduced muscle mass in patients with gastric cancer.

Comparison of the efficacy for early warning systems in predicting obstetric critical illness.

OBJECTIVE: To validate the accuracy of four early warning scores for early identification of women at risk. METHODS: This was a retrospective study of pregnant women admitted in obstetrics Critical Care Unit (ICU). Capacity of the Modified Obstetric Early Warning Score (MOEWS), ICNARC Obstetric Early Warning Score (OEWS), Maternal Early Obstetric Warning System (MEOWS chart), and Maternal Early Warning Trigger (MEWT) were compared in predicting severe maternal morbidity. Area under receiver operator characteristic (AUROC) curve was used to evaluate the predictive performance of scoring system. RESULTS: A total of 352 pregnant women were enrolled and 290 were identified with severe maternal morbidity. MOEWS was more sensitive than MEOWS chart, ICNARC OEWS and MEWT (96.9 % vs. 83.4 %, 66.6 % and 44.8 %). MEWT had the highest specificity (98.4 %), followed by MOEWS (83.9 %), ICNARC OEWS (75.8 %) and MEOWS chart (48.4 %). AUROC of MOEWS, ICNARC OEWS, MEOWS chart, and MEWT for prediction of maternal mortality were 0.91 (95 % CI: 0.874-0.945), 0.765(95 % CI: 0.71-0.82), 0.657(95 % CI: 0.577-0.738), and 0.716 (95 % CI, 0.659-0.773) respectively. MOEWS had the highest AUCs in the discrimination of serious complications in hypertensive disorders, cardiovascular disease, obstetric hemorrhage and infection. For individual vital signs, maximum diastolic blood pressure (DBP), maximum systolic blood pressure (SBP), maximum respiratory rate (RR) and peripheral oxygen saturation (SPO2) demonstrated greater predictive ability. CONCLUSION: MOEWS is more accurate than ICNARC OEWS, MEOWS chart, and MEWT in predicting the deterioration of women. The prediction ability of DBP, SBP, RR and SPO2 are more reliable.

Memory/active T cell activation is associated with immunotherapeutic response in fumarate hydratase-deficient renal cell carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for metastatic patients. RESULTS: In the localized setting, we found that a cell cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS: 17.3 vs. 9.6 months, P=0.016) and OS (median OS: not reached vs. 25.7 months, P=0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

Detection and discrimination of glutathione among biological thiols based on oxalyl dihydrazide decorated sulfur nanodots.

The quantitative detection and discrimination of glutathione (GSH) were achieved based on oxalyl dihydrazide (ODH) decorated sulfur nanodots. ODH resulted in the aggregation and fluorescence quenching of the sulfur nanodots, and GSH selectively triggered fluorescence recovery through forming stronger hydrogen bonds with ODH than other biological thiols.

Integrated lithium niobate microwave photonic processing engine.

Integrated microwave photonics (MWP) is an intriguing technology for the generation, transmission and manipulation of microwave signals in chip-scale optical systems1,2. In particular, ultrafast processing of analogue signals in the optical domain with high fidelity and low latency could enable a variety of applications such as MWP filters3-5, microwave signal processing6-9 and image recognition10,11. An ideal integrated MWP processing platform should have both an efficient and high-speed electro-optic modulation block to faithfully perform microwave-optic conversion at low power and also a low-loss functional photonic network to implement various signal-processing tasks. Moreover, large-scale, low-cost manufacturability is required to monolithically integrate the two building blocks on the same chip. Here we demonstrate such an integrated MWP processing engine based on a 4 inch wafer-scale thin-film lithium niobate platform. It can perform multipurpose tasks with processing bandwidths of up to 67 GHz at complementary metal-oxide-semiconductor (CMOS)-compatible voltages. We achieve ultrafast analogue computation, namely temporal integration and differentiation, at sampling rates of up to 256 giga samples per second, and deploy these functions to showcase three proof-of-concept applications: solving ordinary differential equations, generating ultra-wideband signals and detecting edges in images. We further leverage the image edge detector to realize a photonic-assisted image segmentation model that can effectively outline the boundaries of melanoma lesion in medical diagnostic images. Our ultrafast lithium niobate MWP engine could provide compact, low-latency and cost-effective solutions for future wireless communications, high-resolution radar and photonic artificial intelligence.

Molecular complexity of intraductal carcinoma of the prostate.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.

Self-assembly and aggregation behavior of temperature-controlled modified glycinin and d-galactose colloidal particles.

The molecular structure and morphologies of complex colloidal particles with modified glycine (S-11S) and d-galactose were studied by multispectral, microscopic imaging and chromatographic techniques at different temperatures, and the self-assembly and aggregation mechanisms were determined. Overall, high-temperature-treated S-11S and d-galactose associate at cysteine and phenylalanine sites and self-assemble into colloidal particles of greater stability than glycinin and S-11S via ionic and disulfide bonds. The structure and subunit content of composite colloidal particles were changed. Assessing the sub-microstructure reveals that temperature can regulate the directional aggregation of complex colloidal particles. The elasticity of the complex colloidal particles is maximum enhanced at 95 ℃ as confirmed by the rheological. Thus, the heat-treated aggregation of the soy protein and its complex was evaluated to provide a new theoretical basis for the application of soy protein in gels and other areas and contribute to the design of new soy protein products.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Age and sex differences in the association between neighborhood socioeconomic environment and incident diabetes: Results from the diabetes location, environmental attributes and disparities (LEAD) network.

Objective: Worse neighborhood socioeconomic environment (NSEE) may contribute to an increased risk of type 2 diabetes (T2D). We examined whether the relationship between NSEE and T2D differs by sex and age in three study populations. Research design and methods: We conducted a harmonized analysis using data from three independent longitudinal study samples in the US: 1) the Veteran Administration Diabetes Risk (VADR) cohort, 2) the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, and 3) a case-control study of Geisinger electronic health records in Pennsylvania. We measured NSEE with a z-score sum of six census tract indicators within strata of community type (higher density urban, lower density urban, suburban/small town, and rural). Community type-stratified models evaluated the likelihood of new diagnoses of T2D in each study sample using restricted cubic splines and quartiles of NSEE. Results: Across study samples, worse NSEE was associated with higher risk of T2D. We observed significant effect modification by sex and age, though evidence of effect modification varied by site and community type. Largely, stronger associations between worse NSEE and diabetes risk were found among women relative to men and among those less than age 45 in the VADR cohort. Similar modification by age group results were observed in the Geisinger sample in small town/suburban communities only and similar modification by sex was observed in REGARDS in lower density urban communities. Conclusions: The impact of NSEE on T2D risk may differ for males and females and by age group within different community types.

Correction: Zhu et al. Gait Analysis with Wearables Is a Potential Progression Marker in Parkinson's Disease. Brain Sci. 2022, 12, 1213.

In the original publication [...].

SETD4 inhibits prostate cancer development by promoting H3K27me3-mediated NUPR1 transcriptional repression and cell cycle arrest.

The suppressor of variegation enhancer of zeste-trithorax (SET) domain methyltransferases have been reported to function as key regulators in multiple tumor types by catalyzing histone lysine methylation. Nevertheless, our understanding on the role of these lysine methyltransferases, including SETD4, in prostate cancer (PCa) remains limited. Hence, the specific role of SETD4 in PCa was investigated in this study. The expression of SETD4 in PCa cells and tissue samples was downregulated in PCa cells and tissue specimens, and decreased SETD4 expression led to inferior clinicopathological characteristics in patients with PCa. knockdown of SETD4 facilitated the proliferation of PCa cells and accelerated cell cycle progression. Mechanistically, SETD4 repressed NUPR1 transcription by methylating H3K27 to generate H3K27me3, subsequently inactivated Akt pathway and impeded the tumorigenesis of PCa. Our results highlight that SETD4 prevents the development of PCa by catalyzing the methylation of H3K27 and suppressing NUPR1 transcription, subsequently inactivating the Akt signaling pathway. The findings suggest the potential application of SETD4 in PCa prognosis and therapeutics.

Causal association between placental growth factor and coronary heart disease: a Mendelian randomization study.

OBJECTIVE: Placental growth factor (PlGF), an important polypeptide hormone, plays an important regulatory role in various physiological processes. Observational studies have shown that PlGF is associated with the risk of coronary heart disease (CHD). However, the causal association between PlGF and CHD is unclear at present. This study aimed to investigate the causal association between genetically predicted PlGF levels and CHD. METHODS: Single nucleotide polymorphisms (SNPs) associated with PlGF were selected as instrumental variables (IVs) to evaluate the causal association between genetically predicted circulating PlGF levels and CHD risk by two-sample Mendelian randomization (MR). RESULTS: Inverse variance weighted (IVW) analysis showed that there was a suggestive causal association between genetically predicted PlGF level and the risk of CHD (OR = 0.79, 95% CI: 0.66-0.95, P = 0.011) overall. In addition, PlGF levels had a significant negative causal association with the risk of myocardial infarction (OR = 0.83, 95% CI: 0.72-0.95, P = 0.007). A negative correlation trend was found between PlGF level and the risk of angina pectoris (OR = 0.89, 95% CI: 0.79-1.01, P = 0.067). In addition, PlGF levels had a significant negative association with the risk of unstable angina pectoris (OR = 0.78, 95% CI: 0.64-0.94, P = 0.008). PlGF levels were negatively correlated with CHD events with suggestive significance (OR = 0.89, 95% CI: 0.80-0.99, P = 0.046). CONCLUSION: Genetically predicted circulating PlGF levels are causally associated with the risk of CHD, especially acute coronary syndrome, and PlGF is a potential therapeutic target for CHD.

Integrated bioinformatics analysis and network pharmacology to explore the potential mechanism of Patrinia heterophylla Bunge against acute promyelocytic leukemia.

INTRODUCTION: Current treatment with arsenic trioxide and all-trans retinoic acid has greatly improved the therapeutic efficacy and prognosis of acute promyelocytic leukemia (APL), but may cause numerous adverse effects. Patrinia heterophylla Bunge (PHEB), commonly known as "Mu-Tou-Hui" in China, is effective in treating leukemia. However, no studies have reported the use of PHEB for APL treatment. In this study, we aimed to investigate the potential anticancer mechanism of PHEB against APL. METHODS: Public databases were used to search for bioactive compounds in PHEB, their potential targets, differentially expressed genes associated with APL, and therapeutic targets for APL. The core targets and signaling pathways of PHEB against APL were identified by the protein-protein interaction network, Kaplan-Meier curves, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and compound-target-pathway network analysis. Molecular docking was performed to predict the binding activity between the most active compounds and the key targets. RESULTS: Quercetin and 2 other active components of PHEB may exert anti-APL effects through proteoglycans in cancer, estrogen signaling, and acute myeloid leukemia pathways. We also identified 6 core targets of the bioactive compounds of PHEB, including protein tyrosine phosphatase receptor type C, proto-oncogene tyrosine-protein kinase Src, mitogen-activated protein kinase phosphatase 3 (MAPK3), matrix metalloproteinase-9, vascular endothelial growth factor receptor-2, and myeloperoxidase, most of which were validated to improve the 5-year survival of patients. Molecular docking results showed that the active compound bound well to key targets. CONCLUSION: The results not only predict the active ingredients and potential molecular mechanisms of PHEB against APL, but also help to guide further investigation into the anti-APL application of PHEB.

Bioconjugation of a Fibroblast Activation Protein Targeted Interleukin-4.

Interleukin-4 (IL-4) is an immune-modulating therapeutic with growing potential for the treatment of inflammatory diseases. Current challenges of IL-4 therapy include a low serum half-life and pleiotropic activity, suggesting effective targeting of IL-4. To develop an interleukin-4 bioconjugate with rapid targeting to inflammatory disease sites, we report the chemical synthesis, bioconjugation, and in vitro characterization of a murine interleukin-4 (mIL-4) conjugate decorated with a fibroblast activation protein inhibitor (FAPI). The FAPI targeting moiety features 2,2',2″,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) to allow future biodistribution and imaging studies of the FAPI-mIL-4 bioconjugate. We demonstrated site-specific coupling of mIL-4 and FAPI-DOTA deploying chemo-enzyme and enzyme chemistries with a high purity exceeding 95%. The FAPI-DOTA modified mIL-4 was bioactive with polarization of murine macrophages into the M2 state while maintaining specific binding to FAP on fibroblast cells. Together, these results point to future in vivo use of the FAPI-mIL-4 bioconjugate to assess biodistribution and biological effects in animal models of inflammatory joint disease.

Surmounting Cancer Drug Resistance: New Perspective on RNA-Binding Proteins.

RNA-binding proteins (RBPs), being pivotal elements in both physiological and pathological processes, possess the ability to directly impact RNA, thereby exerting a profound influence on cellular life. Furthermore, the dysregulation of RBPs not only induces alterations in the expression levels of genes associated with cancer but also impairs the occurrence of post-transcriptional regulatory mechanisms. Consequently, these circumstances can give rise to aberrations in cellular processes, ultimately resulting in alterations within the proteome. An aberrant proteome can disrupt the equilibrium between oncogenes and tumor suppressor genes, promoting cancer progression. Given their significant role in modulating gene expression and post-transcriptional regulation, directing therapeutic interventions towards RBPs represents a viable strategy for combating drug resistance in cancer treatment. RBPs possess significant potential as diagnostic and prognostic markers for diverse cancer types. Gaining comprehensive insights into the structure and functionality of RBPs, along with delving deeper into the molecular mechanisms underlying RBPs in tumor drug resistance, can enhance cancer treatment strategies and augment the prognostic outcomes for individuals afflicted with cancer.

The 18th amino acid glycine plays an essential role in maintaining the structural stabilities of γS-crystallin linking with congenital cataract.

γS-crystallin is particularly rich in the embryonic nuclear region and is crucial to the maintenance of lens transparency and optical properties. Gene mutations in crystallin are the main factors leading to congenital hereditary cataracts, which are a major cause of visual impairment in children. Some mutations located in the 18th amino acid glycine of γS-crystallin were reported to be linking with congenital cataracts. However, the pathogenic mechanism has not been elucidated. Interestingly, we previously identified a novel variant of γS-crystallin (c.53G > A; p. G18D) with progressive cortical and sutural congenital cataracts in one Chinese family. In this study, we purified the γS-crystallin wildtype and mutant proteins to investigate the effects of the G18D mutation on the structural stability of γS-crystallin. The results showed that there were tertiary structural differences between the wild-type γS-crystallin and the G18D variant. The mutation significantly impaired the stability of γS-crystallin under environmental stress and promoted aggregation. Furthermore, molecular dynamics (MD) simulations showed that the mutation altered H-bonding and surface electrostatic potential. Significantly decreased stability along with an increased tendency to aggregate under environmental stress may be the major pathogenic factors for cataracts induced by the G18D mutation.