PFOS-induced Sertoli cell injury through c-Jun N-terminal kinase (JNK) - a study by RNA-Seq.

Per- and polyfluoroalkyl substances (PFAS) are a family of "forever chemicals" including PFOS (perfluorooctane sulfonate). These toxic chemicals do not break down in the environment nor in our bodies. In the human body, PFOS and PFOA (perfluoroctanoic acid) have a half-life (T1/2) of about 4-5 years so low daily consumption of these chemicals can accumulate in the human body to a harmful level over a long period. Although the use of PFOS in consumer products was banned in the U.S. in 2022/2023, this forever chemical remains detectable in our tap water and food products. Every American tested has a high level of PFAS in their blood (https://cleanwater.org/pfas-forever-chemicals). In this report, we used a Sertoli cell blood-testis barrier (BTB) model with primary Sertoli cells cultured in vitro with an established functional tight junction (TJ)-permeability barrier that mimicked the BTB in vivo. Treatment of Sertoli cells with PFOS was found to perturb the TJ-barrier, which was the result of cytoskeletal disruption across the cell cytoplasm, disrupting actin and microtubule polymerization. These changes thus affected the proper localization of BTB-associated proteins at the BTB. Using RNA-Seq transcriptome profiling, bioinformatics analysis, and pertinent biochemical and cell biology techniques, it was discovered that PFOS-induced Sertoli cell toxicity through the c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase, SAPK) and its phosphorylated/active form p-JNK signaling pathway. More importantly, KB-R7943 mesylate (KB), a JNK/p-JNK activator, was capable of blocking PFOS-induced Sertoli cell injury, supporting the notion that PFOS-induced cell injury can possibly be therapeutically managed.

Performance evaluation of the digital morphology analyser Sysmex DI-60 for white blood cell differentials in abnormal samples.

Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic samples. We evaluate the efficacy of DI-60 in determining white blood cell (WBC) differentials in normal and abnormal samples in different WBC count. Peripheral blood smears (n = 166) were categorised into normal control and disease groups, and further divided into moderate and severe leucocytosis, mild leucocytosis, normal, mild leukopenia, and moderate and severe leukopenia groups based on WBC count. DI-60 preclassification and verification and manual counting results were assessed using Bland-Altman and Passing-Bablok regression analyses. The Kappa test compared the concordance in the abnormal cell detection between DI-60 and manual counting. DI-60 exhibited notable overall sensitivity and specificity for all cells, except basophils. The correlation between the DI-60 preclassification and manual counting was high for segmented neutrophils, band neutrophils, lymphocytes, and blasts, and improved for all cell classes after verification. The mean difference between DI-60 and manual counting for all cell classes was significantly high in moderate and severe leucocytosis (WBC > 30.0 × 109/L) and moderate and severe leukopenia (WBC < 1.5 × 109/L) groups. For blast cells, immature granulocytes, and atypical lymphocytes, the DI-60 verification results were similar to the manual counting results. Plasma cells showed poor agreement. In conclusion, DI-60 demonstrates consistent and reliable analysis of WBC differentials within the range of 1.5-30.0 × 109. Manual counting was indispensable in examining moderate and severe leucocytosis samples, moderate and severe leukopenia samples, and in enumerating of monocytes and plasma cells.

Near-Infrared Responsive Nanocomposite Hydrogel Dressing with Anti-Inflammation and Pro-Angiogenesis for Wound Healing.

Anti-inflammatory and angiogenesis are two important factors in wound healing. Wound dressings with anti-inflammation and vascularization are essential to address complex interventions, expensive treatments, and uncontrolled release mechanisms. Based on the above considerations, we designed a near-infrared (NIR)-responsive hydrogel dressing, which is composed of mPDA-DFO@LA nanoparticles (mPDA: dopamine hydrochloride nanoparticles, DFO: deferoxamine, LA: lauric acid), valsartan (abbreviated as Va), and dopamine-hyaluronic acid hydrogel. The hydrogel dressing demonstrated injectability, bioadhesive, and photothermal properties. The results indicated the obtained dressing by releasing Va can appropriately regulate macrophage phenotype transformation from M1 to M2, resulting in an anti-inflammatory environment. In addition, DFO encapsulated by LA can be sustainably released into the wound site by NIR irradiation, which further prevents excessive neovascularization. Notably, the results in vivo indicated the mPDA-DFO@LA/Va hydrogel dressing significantly enhanced wound recovery, achieving a healing rate of up to 96% after 11 days of treatment. Therefore, this NIR-responsive hydrogel dressing with anti-inflammation, vascularization, and on-demand programmed drug release will be a promising wound dressing for wound infection.

Exploring the Pathogenesis and Treatment of PSD from the Perspective of Gut Microbiota.

Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and treatment of PSD is still in the infancy stage. Patients with PSD often exhibit gastrointestinal symptoms; therefore the role of gut microbiota in the pathophysiology and potential treatment effects of PSD has become a hot topic of research. In this review, describe the research on the pathogenesis and therapy of PSD. We also describe how the gut microbiota influences neurotransmitters, the endocrine system, energy metabolism, and the immune system. It was proposed that the gut microbiota is involved in the pathogenesis and treatment of PSD through the regulation of neurotransmitter levels, vagal signaling, hypothalamic-pituitary-adrenal axis activation and inhibition, hormone secretion and release, in addition to immunity and inflammation.

A universal electrochemical biosensor based on CRISPR/Cas12a and a DNA tetrahedron for ultrasensitive nucleic acid detection.

Herein, a universal nucleic acid analysis platform was constructed for sensitive and accurate detection of miRNA-155 and ctDNA using isothermal amplification-assisted CRISPR/Cas12a and a tetrahedral DNA nanostructure (TDN) supported sensing interface. Under the optimal experimental conditions, the prepared sensor achieved specific detection of miRNA-155 and ctDNA at as low as aM levels in 2.6 h. Furthermore, the platform was also successfully applied to human serum sample recovery experiments and cancer cell lysates, demonstrating outstanding reliability and accuracy. We firmly believe that this work provides a universal, sensitive, and practical tool for early clinical diagnosis.

Triptolide exposure triggers testicular vacuolization injury by disrupting the Sertoli cell junction and cytoskeletal organization via the AKT/mTOR signaling pathway.

BACKGROUND: Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains largely obscure. METHODS: Male mice were subjected to TP at doses of 15, 30, and 60 µg/kg for 35 consecutive days. Primary Sertoli cells were isolated from 20-day-old rat testes and exposed to TP at concentrations of 0, 40, 80, 160, 320, and 640 nM. A Biotin tracer assay was conducted to assess the integrity of the blood-testis barrier (BTB). Transepithelial electrical resistance (TER) assays were employed to investigate BTB function in primary Sertoli cells. Histological structures of the testes and epididymides were stained with hematoxylin and eosin (H&E). The expression and localization of relevant proteins or pathways were assessed through Western blotting or immunofluorescence staining. RESULTS: TP exposure led to dose-dependent testicular injuries, characterized by a decreased organ coefficient, reduced sperm concentration, and the formation of vacuolization damage. Furthermore, TP exposure disrupted BTB integrity by reducing the expression levels of tight junction (TJ) proteins in the testes without affecting basal ectoplasmic specialization (basal ES) proteins. Through the TER assay, we identified that a TP concentration of 160 nM was optimal for elucidating BTB function in primary Sertoli cells, correlating with reductions in TJ protein expression. Moreover, TP exposure induced changes in the distribution of the BTB and cytoskeleton-associated proteins in primary Sertoli cells. By activating the AKT/mTOR signaling pathway, TP exposure disturbed the balance between mTORC1 and mTORC2, ultimately compromising BTB integrity in Sertoli cells. CONCLUSION: This investigation sheds light on the impacts of TP exposure on testes, elucidating the mechanism by which TP exposure leads to testicular vacuolization injury and offering valuable insights into comprehending the toxic effects of TP exposure on testes.

SARS-CoV-2 infection, vaccination and in vitro fertilization treatment: A prospective cohort study.

BACKGROUND: The impact of COVID-19 on reproductive health is controversial. The association between female SARS-CoV-2 infection and laboratory and pregnancy outcomes following subsequent in vitro fertilization (IVF) treatment remains unclear. This study aimed to investigate the relationship between IVF treatment at different time intervals after SARS-CoV-2 infection and reproductive outcomes. METHODS: A prospective cohort study of 920 IVF cycles post-SARS-CoV-2 infection was conducted. Modified Poisson regression and logistic regression models were utilized to evaluate oocyte- and embryo-related outcomes as well as clinical outcomes. Stratified analyses were also performed based on the vaccination status of the female participants. RESULTS: SARS-CoV-2 infection within three months was associated with reduced available [Adjusted RR (aRR): 0.96, 95 %CI: 0.91-1.00] and top-quality embryos (aRR: 0.90, 95 %CI: 0.83-0.98) in subsequent IVF treatment. Among patients failing to finish the three-dose vaccination, the interval between SARS-CoV-2 infection and cycle initiation of less than 90 days was associated with a lower number of oocytes retrieval (aRR: 8.81, 95 %CI: 8.24-9.41 vs aRR: 9.64, 95 %CI: 9.06-10.25), available embryos (aRR: 0.93, 95 %CI: 0.88-0.99), and top-quality embryos (aRR: 0.81, 95 %CI: 0.72-0.91) rather than among fully vaccinated women. Moreover, COVID-19 infection was not associated with biochemical pregnancy, clinical pregnancy, embryo implantation, and early abortion either in fresh embryo transfer (ET) or frozen ET. CONCLUSIONS: This study indicated that initiating IVF treatment within 90 days of SARS-CoV-2 infection might reduce the likelihood of obtaining available and top-quality embryos, especially among those who had not completed the three-dose vaccination. Nevertheless, female COVID-19 infection did not affect pregnancy or early abortion. Further rigorously designed studies are required to support these findings.

A Novel CRISPR/Cas12a-Mediated Ratiometric Dual-Signal Electrochemical Biosensor for Ultrasensitive and Reliable Detection of Circulating Tumor Deoxyribonucleic Acid.

Circulating tumor DNA (ctDNA) holds great promise as a noninvasive biomarker for cancer diagnosis, treatment, and prognosis. However, the accurate and specific quantification of low-abundance ctDNA in serum remains a significant challenge. This study introduced, for the first time, a novel exponential amplification reaction (EXPAR)-assisted CRISPR/Cas12a-mediated ratiometric dual-signal electrochemical biosensor for ultrasensitive and reliable detection of ctDNA. To implement the dual-signal strategy, a signal unit (ssDNA-MB@Fc/UiO-66-NH2) was prepared, consisting of methylene blue-modified ssDNA as the biogate to encapsulate ferrocene signal molecules within UiO-66-NH2 nanocarriers. The presence of target ctDNA KRAS triggered EXPAR amplification, generating numerous activators for Cas12a activation, resulting in the cleavage of ssDNA-P fully complementary to the ssDNA-MB biogate. Due to the inability to form a rigid structure dsDNA (ssDNA-MB/ssDNA-P), the separation of ssDNA-MB biogate from the UiO-66-NH2 surface was hindered by electrostatic interactions. Consequently, the supernatant collected after centrifugation exhibited either no or only a weak presence of Fc and MB signal molecules. Conversely, in the absence of the target ctDNA, the ssDNA-MB biogate was open, leading to the leakage of Fc signal molecules. This clever ratiometric strategy with Cas12a as the "connector", reflecting the concentration of ctDNA KRAS based on the ratio of the current intensities of the two electroactive signal molecules, enhanced detection sensitivity by at least 60-300 times compared to single-signal strategies. Moreover, this strategy demonstrated satisfactory performance in ctDNA detection in complex human serum, highlighting its potential for cancer diagnosis.

Versatile design for temporal shape control of high-power nanosecond pulsed fiber laser amplifier.

This research proposed a novel pulse-shaping design for directly shaping distorted pulses after the amplification. Based on the principle of the design we made a pulse shaper. With this pulse shaper, we successfully manipulate the pulse's leading edge and width to achieve an 'M'-shaped waveform in an amplification system. Comparative experiments were conducted within this system to compare the output with and without the integration of the pulse shaper. The results show a significant suppression of the nonlinear effect upon adding the pulse shaper. This flexible and effective pulse shaper can be easily integrated into a high-power all-fiber system, supplying the capability to realize the desired output waveform and enhance the spectral quality.

Evaluating How Different Drying Techniques Change the Structure and Physicochemical and Flavor Properties of Gastrodia elata.

We evaluated the drying characteristics and structure, as well as the physicochemical and flavor properties, of G. elata treated by hot-air drying (HAD), vacuum drying (VD), freeze drying (FD), microwave drying (MD), and microwave vacuum drying (MVD). We found that MD and MVD showed the shortest drying times, while FD and MVD were able to better retain the active ingredients and color of the samples. However, the different drying methods did not change the internal structure of G. elata, and its main components did not fundamentally change. In addition, E-nose and HS-SPME-GC-MS effectively differentiated the volatile components, and 36 compounds were detected by HS-SPME-GC-MS. Of these samples, alcohols and aldehydes were the main substances identified. In particular, MVD samples possessed the most species of organic volatiles, but the FD method effectively eliminated pungent odors from the G. elata. Overall, MVD shows the most obvious advantages, improving drying rate while maintaining the original shape, color, and active components in G. elata. Ultimately, MVD is the preferred method to obtain high-quality dried G. elata, and our drying-method characterizations can be used to investigate similar structural and chemical changes to similar herbs in the future.

The Planar Cell Polarity Protein Fat1 in Sertoli Cell Function.

Fat (FAT atypical cadherin) and Dchs (Dachsous cadherin-related protein) in adjacent Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid interfaces create an important intercellular bridge whose adhesive function is in turn supported by Fjx1, a nonreceptor Ser/Thr protein kinase. This concept is derived from earlier studies of Drosophila, which has been confirmed in this and earlier reports as well. Herein, we use the approach of knockdown of Fat1 by RNAi using primary cultures of Sertoli cells that mimicked the blood-testis barrier (BTB) in vivo, and a series of coherent experiments including functional assays to monitor the Sertoli cell tight junction (TJ) permeability barrier and a functional in vitro TJ integrity assay to assess the role of Fat1 in the testis. It was shown that planar cell polarity (PCP) protein Fat1 affected Sertoli cell function through its modulation of actin and microtubule cytoskeletal function, altering their polymerization activity through the Fat1/Fjx1 complex. Furthermore, Fat1 is intimately associated with ß-catenin and α-N-catenin, as well as with Prickle 1 of the Vangl1/Prickle 1 complex, another PCP core protein to support intercellular interactions to confer PCP. In summary, these findings support the notion that the Fat:Dchs and the Vangl2:Fzd PCP intercellular bridges are tightly associated with basal ES/TJ structural proteins to stabilize PCP function at the Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid interface to sustain spermatogenesis.

Impact of SARS-CoV2 infection on gut microbiota dysbiosis.

The composition and function of the gut microbiota constantly influence health. Disruptions in this delicate balance, termed gut microbiota dysbiosis, have been implicated in various adverse health events. As the largest global epidemic since 1918, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had devastating consequences. While the primary impact of Corona Virus Disease 2019 (COVID-19) has been on the respiratory system, a growing body of research has unveiled the significant involvement of the gastrointestinal tract as well. Emerging evidence underscores notable alterations in the gut microbiome of COVID-19 patients. In addition, the gut microbiome is also characterized by an abundance of opportunistic pathogens, which is related to disease manifestations of COVID-19 patients. The intricate bidirectional interaction between the respiratory mucosa and the gut microbiota, known as the gut-lung axis, emerges as a crucial player in the pathological immune response triggered by SARS-CoV-2. Here, we discuss microbiota-based gut characteristics of COVID-19 patients and the long-term consequences of gut microbiota dysregulation. These insights could potentially transform the development of long-term interventions for COVID-19, offering hope for improved outcomes and enhanced patient recovery.

Transketolase drives the development of aortic dissection by impairing mitochondrial bioenergetics.

AIM: Aortic dissection (AD) is a disease with rapid onset but with no effective therapeutic drugs yet. Previous studies have suggested that glucose metabolism plays a critical role in the progression of AD. Transketolase (TKT) is an essential bridge between glycolysis and the pentose phosphate pathway. However, its role in the development of AD has not yet been elucidated. In this study, we aimed to explore the role of TKT in AD. METHODS: We collected AD patients' aortic tissues and used high-throughput proteome sequencing to analyze the main factors influencing AD development. We generated an AD model using BAPN in combination with angiotensin II (Ang II) and pharmacological inhibitors to reduce TKT expression. The effects of TKT and its downstream mediators on AD were elucidated using human aortic vascular smooth muscle cells (HAVSMCs). RESULTS: We found that glucose metabolism plays an important role in the development of AD and that TKT is upregulated in patients with AD. Western blot and immunohistochemistry confirmed that TKT expression was upregulated in mice with AD. Reduced TKT expression attenuated AD incidence and mortality, maintained the structural integrity of the aorta, aligned elastic fibers, and reduced collagen deposition. Mechanistically, TKT was positively associated with impaired mitochondrial bioenergetics by upregulating AKT/MDM2 expression, ultimately contributing to NDUFS1 downregulation. CONCLUSION: Our results provide new insights into the role of TKT in mitochondrial bioenergetics and AD progression. These findings provide new intervention options for the treatment of AD.

High repetition frequency tunability active Q-switched all-fiber laser by multi-gain sub-rings smoothing multipeak pulse and suppressing ASE self-saturation.

This paper provides a method to effectively suppress the severe ASE self-saturation when achieving high repetition frequency tunability with high output power and narrow pulse width in active Q-switched all-fiber lasers. By studying the regularity of the system's multi-stable state, we first ensured that the laser system operated in a steady state. Then output avoids uneven distribution of pulse energy or missing pulses due to period bifurcation state or chaos state. By adding multiple gain sub-rings within the cavity, the sub-ring structure itself indirectly mitigates the ASE self-saturation while smoothing the pulse. The method will avoid the severe power loss caused by traditional smoothing methods by adjusting the AOM rising edge time. It will also avoid lowering the ASE lasing threshold at high repetition frequency. Meanwhile, the intra-cavity backward ASE can be effectively absorbed by inserting the gain fiber in the sub-rings to directly mitigate the ASE self-saturation. The system's continuously adjustable repetition frequency can be as high as over 300 kHz. It ensures that output power above the watt level and a < 0.2 nm narrow bandwidth can be maintained while tuning the repetition frequency. The narrowest smoothing pulse width of 28 ns has been reached.

Modulation of Acute Intestinal Inflammation by Dandelion Polysaccharides: An In-Depth Analysis of Antioxidative, Anti-Inflammatory Effects and Gut Microbiota Regulation.

Acute colitis is a complex disease that can lead to dysregulation of the gut flora, inducing more complex parenteral diseases. Dandelion polysaccharides (DPSs) may have potential preventive and therapeutic effects on enteritis. In this study, LPS was used to induce enteritis and VC was used as a positive drug control to explore the preventive and therapeutic effects of DPS on enteritis. The results showed that DPS could repair the intestinal barrier, down-regulate the expression of TNF-α, IL-6, IL-1ß, and other pro-inflammatory factors, up-regulate the expression of IL-22 anti-inflammatory factor, improve the antioxidant capacity of the body, and improve the structure of intestinal flora. It is proved that DPS can effectively prevent and treat LPS-induced acute enteritis and play a positive role in promoting intestinal health.

Orienting Group Directed Cascade Borylation for Efficient One-Shot Synthesis of 1,4-BN-Doped Polycyclic Aromatic Hydrocarbons as Narrowband Organic Emitters.

1,4-BN-doped polycyclic aromatic hydrocarbons (PAHs) have emerged as very promising emitters in organic light-emitting diodes (OLEDs) due to their narrowband emission spectra that may find application in high-definition displays. While considerable research has focused on investigating the properties of these materials, less attention has been placed on their synthetic methodology. Here we developed an efficient synthetic method for 1,4-BN-doped PAHs, which enables sustainable production of narrowband organic emitting materials. By strategically introducing substituents, such as methyl, tert-butyl, phenyl, and chloride, at the C5 position of the 1,3-benzenediamine substrates, we achieved remarkable regioselective borylation in the para-position of the substituted moiety. This approach facilitated the synthesis of a diverse range of 1,4-BN-doped PAHs emitters with good yields and exceptional regioselectivity. The synthetic method demonstrated excellent scalability for large-scale production and enabled late-stage transformation of the borylated products. Mechanistic investigations provided valuable insights into the pivotal roles of electron effect and steric hindrance effect in achieving highly efficient regioselective borylation. Moreover, the outstanding device performance of the synthesized compounds 10 b and 6 z, underscores the practicality and significance of the developed method.

Factors that influence the intent to pursue a master's degree: evidence from Shandong Province, China.

Introduction: In recent years, the pursuit of a master's degree has become a social phenomenon of wide concern. It is essential to understand why large number of students choose to pursue master's degree. This study aims to empirically analyze the factors that influence the intent to pursue a master's degree. Method: Based on the extended theory of planned behavior, this study conducts a questionnaire survey of university students in Shandong Province, which has had the highest number of people taking the postgraduate entrance examination in China for several years. A total of 440 questionnaires were finally collected, including 417 valid questionnaires. And then ordinary least squares (OLS) regression was used to analyze the factors that influence the intent to pursue a master's degree. Results: In general, the intent to pursue a master's degree is positively influenced by attitude (ß = 0.161, p < 0.01) and subjective norms (ß = 0.208, p < 0.01), and negatively influenced by risk perception (ß = -0.084, p < 0.05). Compared with male students, female students' intent is more likely to be influenced by risk perception (ß = -0.144, p < 0.05) and social factors (ß = 0.140, p < 0.05). The intent of upperclass students tends to be positively influenced by perceived behavioral control (ß = 0.125, p < 0.05), whereas the negative impact of risk perception (ß = -0.219, p < 0.05) on the intent is significant for underclass students. The intent of students in rural areas are more sensitive to risk perception (ß = -0.194, p < 0.01) than those of students in cities. In private universities, social factors (ß = 0.445, p < 0.05) significantly affect the intent to pursue a master's degree. In ordinary public universities, the intent of students is more likely to be influenced by risk perception (ß = -0.082, p < 0.05). Conclusion: The study is helpful to strengthen the understanding of the influencing factors of the intent to pursue a master's degree. In general, the intent to pursue a master's degree is mainly influenced by attitude, subjective norms and risk perception. Moreover, the influencing factors vary among different groups (e.g., female vs. male, rural areas vs. cities). Furthermore, attitude, subjective norms, perceived behavioral control, risk perception, and social factors have greater impacts on the intent of students from low-income households than those from high-income households. This study can provide policy implications for universities to take targeted educational measures to encourage students to make a choice that suits their own development after graduation.

Theoretical insights into the enantiodivergence induced by chiral phosphoric acid catalysis with a Lewis acid for the synthesis of N-N axially chiral atropisomers.

A detailed theoretical mechanistic investigation on chiral phosphoric acid (CPA)-catalyzed Paal-Knorr reactions, in the presence and absence of a Lewis acid, for the synthesis of N-N axially chiral atropisomers is described herein. Density functional theory (DFT) studies elucidate that in the absence of a Lewis acid, CPA catalyzes both the initial cyclization and the subsequent dehydroxylation processes, ambiguously identified as the rate-determining step in the reactions. Conversely, when a Lewis acid participates in the reaction, it facilitates the second dehydroxylation process with a significantly lower energy barrier, thereby reversing the rate-determining step to the initial cyclization step. It is noteworthy that in the case of N-aminoindoles, both the S-configurational transition state TS1 in the cyclization step and TS2 in the dehydroxylation process are favourable. In contrast, for the synthesis of a bispyrrole, the R-configurational TS1 and the S-configurational TS2 are dominant. Therefore, the enantiodivergence observed is essentially induced by the reversed rate-determining steps in the absence or presence of a Lewis acid in the case of a bispyrrole. Furthermore, the non-covalent interaction (NCI) and atoms-in-molecules (AIM) analysis of the TS structures reveal that the non-covalent interactions play a pivotal role in determining the enantiodivergence observed in these reactions.

Secondary analysis of newly diagnosed type 2 diabetes subgroups and treatment responses in the MARCH cohort.

OBJECTIVE: To incorporate new clusters in the MARCH (Metformin and AcaRbose in Chinese patients as the initial Hypoglycemic treatment) cohort of newly diagnosed type 2 diabetes (T2D) patients and compare the anti-glycemic effects of metformin and acarbose across different clusters. METHODS: K-means cluster analysis was performed based on six clinical indicators. The diabetic clusters in the MARCH cohort were retrospectively associated with the response to metformin and acarbose. RESULTS: A total of 590 newly diagnosed T2D patients were classified by data-driven clusters into the MARD (mild obesity-related diabetes) (34.1 %), MOD (mild obesity-related diabetes) (34.1 %), SIDD (severe insulin-deficient diabetes) (20.3 %) and SIRD (severe insulin-resistant diabetes) (11.5 %) subgroups at baseline. At 24 and 48 weeks, 346 participants had finished the follow-up. After the adjustment of age, gender, weight, baseline HbA1c, baseline fasting glucose and 2-h postprandial blood glucose (2hPG), metformin mainly decreased the fasting glucose (0.07 ± 0.89 vs -0.26 ± 0.83, P = 0.043) in the MARD subgroup presented with OGTT (oral glucose tolerance test) results compared with acarbose group at 24 weeks. Acarbose led to a greater decrease in 2hPG in the MOD subgroup compared with metformin group (0.08 ± 0.86 vs -0.24 ± 0.92, P = 0.037) at 24 weeks. There was a also significant interaction between cluster and treatment efficacy in HbA1c (glycated hemoglobin) reduction in metformin and acarbose groups at 24 and 48 weeks (pinteraction<0.001). CONCLUSIONS: Metformin and acarbose affected different metabolic variables depending on the diabetes subtype.