Background: The metabolic score for insulin resistance (METS-IR) has emerged as a noninsulin-based index for the approximation of insulin resistance (IR), yet longitudinal evidence supporting the utility of METS-IR in the primary prevention of type 2 diabetes mellitus (T2DM) remains limited. Objective: We aimed to investigate the longitudinal association between METS-IR, which combines fasting plasma glucose (FPG), lipid profiles, and anthropometrics that can be routinely obtained in resource-limited primary care settings, and the incidence of new-onset T2DM. Methods: We conducted a closed-cohort analysis of a nationwide, prospective cohort of 7583 Chinese middle-aged and older adults who were free of T2DM at baseline, sampled from 28 out of 31 provinces in China. We examined the characteristics of participants stratified by elevated blood pressure (BP) at baseline and new-onset T2DM at follow-up. We performed Cox proportional hazard regression analysis to explore associations of baseline METS-IR with incident T2DM in participants overall and in participants stratified by baseline BP. We also applied net reclassification improvement and integrated discrimination improvement to examine the incremental value of METS-IR. Results: During a mean follow-up period of 6.3 years, T2DM occurred in 527 participants, among which two-thirds (332/527, 62.9%; 95% CI 58.7%-67.1%) had baseline FPG<110 mg/dL. A SD unit increase in baseline METS-IR was associated with the first incidence of T2DM (adjusted hazard ratio [aHR] 1.33, 95% CI 1.22-1.45; P<.001) in all participants. We obtained similar results in participants with normal baseline BP (aHR 1.41, 95% CI 1.22-1.62; P<.001) and elevated baseline BP (aHR 1.29, 95% CI 1.16-1.44; P<.001). The predictive capability for incident T2DM was improved by adding METS-IR to FPG. In study participants with new-onset T2DM whose baseline FPG was <126 mg/dL and <110 mg/dL, 62.9% (332/527; 95% CI 60%-65.9%) and 58.1% (193/332; 95% CI 54.3%-61.9%) of participants had baseline METS-IR above the cutoff values, respectively. Conclusions: METS-IR was significantly associated with new-onset T2DM, regardless of baseline BP level. Regular monitoring of METS-IR on top of routine blood glucose in clinical practice may add to the ability to enhance the early identification of primary care populations at risk for T2DM.

The metabolic score for insulin resistance (METS-IR) was recently proposed as a non-insulin-based, novel index for assessing insulin resistance (IR) in the Western population. However, evidence for the link between METS-IR and prediabetes or type 2 diabetes mellitus (T2DM) among the elderly Chinese population was still limited. We aimed to investigate the associations between METS-IR and prediabetes or T2DM based on large-scale, cross-sectional, routine physical examination data. In a total of 18,112 primary care service users, an increased METS-IR was independently associated with a higher prevalence of prediabetes (adjusted odds ratio [aOR] = 1.457, 95% confidence interval [CI]: 1.343 to 1.581, p < 0.001) and T2DM (aOR = 1.804, 95%CI: 1.720 to 1.891, p < 0.001), respectively. The aOR for prediabetes in subjects with the highest quartile of METS-IR was 3.060-fold higher than that in those with the lowest quartile of METS-IR. The aOR for T2DM in subjects with the highest quartile of METS-IR was 6.226-fold higher than that in those with the lowest quartile of METS-IR. Consistent results were obtained in subgroup analyses. Our results suggested that METS-IR was significantly associated with both prediabetes and T2DM. The monitoring of METS-IR may add value to early identification of individuals at risk for glucose metabolism disorders in primary care.

Background: Visceral adipose tissue plays an active role in the pathogenesis of type 2 diabetes and vascular dysfunction. The lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese VAI (CVAI) have been proposed as simple and validated surrogate indices for measuring visceral adipose tissue. However, the evidence from prospective studies on the associations between these novel indices of visceral obesity and diabetic retinopathy (DR) remains scant. Objective: This study aimed to investigate the longitudinal associations of LAP, VAI, and CVAI with incident DR in Chinese patients with diabetes. Methods: This was a prospective cohort study conducted in Guangzhou in southern China. We collected baseline data between November 2017 and July 2020, while on-site follow-up visits were conducted annually until January 2022. The study participants consisted of 1403 patients with a clinical diagnosis of diabetes, referred from primary care, who were free of DR at baseline. The LAP, VAI, and CVAI levels were calculated by sex-specific equations based on anthropometric and biochemical parameters. DR was assessed using 7-field color stereoscopic fundus photographs and graded according to the modified Airlie House Classification scheme. Time-dependent Cox proportional hazard models were constructed to estimate the hazard ratios with 95% CIs. Restricted cubic spline curves were fitted to examine the dose-response relationship between the 3 indices of visceral obesity and new-onset DR. Subgroup analyses were performed to investigate the potential effect modifiers. Results: The mean age of study participants was 64.5 (SD 7.6) years, and over half (816/1403, 58.2%) were female. During a median follow-up of 2.13 years, 406 DR events were observed. A 1-SD increment in LAP, VAI, or CVAI was consistently associated with increased risk for new-onset DR, with a multivariable‑adjusted hazard ratio of 1.24 (95% CI 1.09-1.41; P=.001), 1.22 (95% CI 1.09-1.36; P<.001), and 1.48 (95% CI 1.19-1.85; P=.001), respectively. Similar patterns were observed across tertiles in LAP (P for trend=.001), VAI (P for trend<.001), and CVAI (P for trend=.009). Patients in the highest tertile of LAP, VAI, and CVAI had an 84%, 86%, and 82% higher hazard of DR, respectively, compared to those in the lowest tertile. A nonlinear dose-response relationship with incident DR was noted for LAP and VAI (both P for nonlinearity<.05), but not for CVAI (P for nonlinearity=.51). We did not detect the presence of effect modification by age, sex, duration of diabetes, BMI, or comorbidity (all P for interaction>.10). Conclusions: Visceral obesity, as measured by LAP, VAI, or CVAI, is independently associated with increased risk for new-onset DR in Chinese patients with diabetes. Our findings may suggest the necessity of incorporating regular monitoring of visceral obesity indices into routine clinical practice to enhance population-based prevention for DR.

5'-Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway and has been reported to suppress tumorigenesis. The MTAP gene is located at 9p21, a chromosome region often deleted in breast cancer (BC). However, the clinical and biological significance of MTAP in BC is still unclear. Here, we reported that MTAP was frequently downregulated in 41% (35/85) of primary BCs and 89% (8/9) of BC cell lines. Low expression of MTAP was significantly correlated with a poor survival of BC patients (P=0.0334). Functional studies showed that MTAP was able to suppress both in vitro and in vivo tumorigenic ability of BC cells, including migration, invasion, angiogenesis, tumor growth and metastasis in nude mice with orthotopic xenograft tumor of BC. Mechanistically, we found that downregulation of MTAP could increase the polyamine levels by activating ornithine decarboxylase (ODC). By treating the MTAP-repressing BC cells with specific ODC inhibitor Difluoromethylornithine (DFMO) or treating the MTAP-overexpressing BC cells with additional putrescine, metastasis-promoting or -suppressing phenotype of these MTAP-manipulated cells was significantly reversed, respectively. Taken together, our data suggested that MTAP has a critical metastasis-suppressive role by tightly regulating ODC activity in BC cells, which may serve as a prominent novel therapeutic target for advanced breast cancer treatment.

Background: Plants are always exposed to dynamic light. The photosynthetic light use efficiency of leaves is lower in dynamic light than in uniform irradiance. Research on the influence of environmental factors on dynamic photosynthesis is very limited. Nitrogen is critical for plants, especially for photosynthesis. Low nitrogen (LN) decreases ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and thus limits photosynthesis. The decrease in Rubisco also delays photosynthetic induction in LN leaves; therefore, we hypothesized that the difference of photosynthetic CO₂ fixation between uniform and dynamic light will be greater in LN leaves compared to leaves with sufficient nitrogen supply. Results: To test this hypothesis, soybean plants were grown under low or high nitrogen (HN), and the photosynthetic gas exchange, enzyme activity and protein amount in leaves were measured under uniform and dynamic light. Unexpectedly, dynamic light caused less photosynthetic suppression, rather than more, in LN leaves than in HN leaves. The underlying mechanism was also clarified. Short low-light (LL) intervals did not affect Rubisco activity but clearly deactivated fructose-1,6-bisphosphatase (FBPase) and sedoheptulose-1,7-bisphosphatase (SBPase), indicating that photosynthetic induction after a LL interval depends on the reactivation of FBPase and SBPase rather than Rubisco. In LN leaves, the amount of Rubisco decreased more than FBPase and SBPase, so FBPase and SBPase were present in relative excess. A lower fraction of FBPase and SBPase needs to be activated in LN leaves for photosynthesis recovery during the high-light phase of dynamic light. Therefore, photosynthetic recovery is faster in LN leaves than in HN leaves, which relieves the photosynthetic suppression caused by dynamic light in LN leaves. Conclusions: Contrary to our expectations, dynamic light caused less photosynthetic suppression, rather than more, in LN leaves than in HN leaves of soybean. This is the first report of a stress condition alleviating the photosynthetic suppression caused by dynamic light.

Background: The physical process of axial length growth among children and its role in the occurrence of myopia remain insufficiently explored. In this study, we investigate the patterns of ocular axial growth among persistent myopia (PM) and persistent non-myopia (PNM) children aged 3 to 15 years. Methods: A group of 6353 children aged 3 to 15 years, selected from rural schools in China, were followed up annually for 2 years. Biometric measurements including axial length (AL) and spherical equivalent refraction (SER) were obtained. Body height was recorded. Children were divided into two groups: PM group defined as SER of −0.50 D or less; PNM group defined as −0.50 D < SER < +3.0 D during follow-up. Results: Annual AL growth was fairly consistent for PNM eyes of children aged 3 to 11 years and then reduced significantly (independent t test, p < 0.001) for children aged 12 years and older. This pattern of AL changes was similar for PM children, although the AL growth was greater among them. Among children aged 6 and older, body height change was concomitant to AL growth (p < 0.01) and SER myopic shift (p < 0.001) until reaching 12 years old (p = 0.308 and p = 0.679, respectively). Conclusions: Stature growth and AL growth are both remarkable and consistent and concomitant but start to attenuate when the children reach 10 to 12 years old among emmetropic children. This observation suggests that AL growth is driven by physical development until 12 years old, whereas its excessive growth is dominated by myopia development.