Effects of partial reduction of polystyrene micro-nanoplastics on the immunity, gut microbiota and metabolome of mice.

Microplastic (MP) and nanoplastic (NP) could cause gut microbiota alterations. Although micro/nanoplastic (MNP) degradation is attracting increasing scientific interest, the evaluation of MNP reduction in gut needs to be further investigated. This study aimed to determine whether partial reduction of polystyrene MNP in gut could affect the immunity, gut microbiota and metabolome of mice. Serum eotaxin/CCL11 was at a lower level in the mice exposed to 200 µg and 500 µg NP (i.e., 2NP and 5NP groups, respectively) compared to those exposed to 500 µg MP (i.e., 5 MP group), while serum IL-2 and IL-4 were both greater in the 5NP group compared to the 5 MP group. The gut bacterial alpha diversity, fungal diversity and evenness were all similar among the MNP and control groups. However, the gut fungal richness was greater in both the 5NP and 5 MP groups compared to the control group. The gut bacterial and fungal compositions were both different between the MNP and control groups. Multiple gut bacteria and fungi showed different levels between the 2NP and 5NP groups, as well as between the 2NP and 5 MP groups. Increased Staphylococcus and decreased Glomus were determined in the 2NP group compared to both the 5NP and 5 MP groups. A Lactobacillus phylotype was found as the sole gatekeeper in the bacterial network of the 2NP group, while a Bifidobacterium phylotype contributed most to the stability of the bacterial networks of both the 5NP and 5 MP groups. Multiple differential gut metabolic pathways were found between the 2NP and 5NP/5 MP groups, and mTOR signaling pathway was largely upregulated in the 2NP group compared to both the 5NP and 5 MP groups. The relevant results could help with the evaluation of partial reduction of MNP in gut.

Carbon dots stabilized photoluminescent blue phase liquid crystals.

Blue phase liquid crystals (BPLCs) have significant potential in the field of liquid crystal displays (LCDs) and are proposed as potential next-generation of LCDs candidates. However, BPLCs do not emit light directly and need an extra backlight device. As a result, the blue phase liquid crystal display retains the disadvantages of low brightness and low energy efficiency, which remarkably limit its application. Recently, as a kind of novel fluorescent carbon nanomaterials, carbon dots (CDs) have captured considerable attention because of their excellent optical properties. Here, CDs were directly synthesized by a simple solvothermal method and introduced into BPLCs. By combining the excellent optical properties of CDs with the blue phase liquid crystal system, the photoluminescent blue phase liquid crystals (CDs-BPLCs) with self-photoluminescence are prepared. Meanwhile, the stability of BPLCs can be improved by CDs. Such CDs-BPLCs have enormous potential in the development of novel energy-saving display devices.

Engineering of cyclodextrin glycosyltransferase improves the conversion efficiency of rebaudioside A to glucosylated steviol glycosides and increases the content of short-chain glycosylated steviol glycoside.

BACKGROUND: Compared with steviol glycosides, the taste of glucosylated steviol glycosides is better and more similar to that of sucrose. At present, cyclodextrin glucanotransferase (CGTase) is primarily used to catalyze the conversion of steviol glycosides to glucosylated steviol glycosides, with soluble starch serving as a glycosyl donor. The main disadvantages of enzymatic transglycosylation are the limited number of enzymes available, the low conversion rates that result in low yields, and the lack of selectivity in the degree of glycosylation of the products. In order to fill these gaps, the proteome of Alkalihalobacillus oshimensis (also named Bacillus oshimensis) was used for mining novel CGTases. RESULTS: Here, CGTase-15, a novel ß-CGTase with a wide pH adaptation range, was identified and characterized. The catalyzed product of CGTase-15 tasted better than that of the commercial enzyme (Toruzyme® 3.0 L). In addition, two amino acid sites, Y199 and G265, which play important roles in the conversion of steviol glycosides to glucosylated steviol glycosides were identified by site-directed mutagenesis. Compared with CGTase-15, CGTase-15-Y199F mutant significantly increased the conversion rate of rebaudioside A (RA) to glucosylated steviol glycosides. Compared with CGTase-15, the content of short-chain glycosylated steviol glycosides catalyzed by CGTase-15-G265A mutant was significantly increased. Moreover, the function of Y199 and G265 was verified in other CGTases. The above mutation pattern has also been applied to CGTase-13 (a CGTase discovered by our laboratory with great potential in the production of glycosylated steviol glycosides), confirming that the catalytic product of CGTase-13-Y189F/G255A mutant has a better taste than that of CGTase-13. CONCLUSIONS: This is the first report on the improvement of the sensory profiles of glycosylated steviol glycosides through site-directed mutagenesis of CGTase, which is significant for the production of glycosylated steviol glycosides.

Efficient Bioconversion of Stevioside and Rebaudioside A to Glucosylated Steviol Glycosides Using an Alkalihalobacillus oshimesis-Derived Cyclodextrin Glucanotransferase.

The enzymatic transglycosylation of steviol glycosides can improve the edulcorant quality of steviol glycosides. Cyclodextrin glucanotransferase (CGTase) is one of the most popular glucanotransferases applied in this reaction. Herein, the CGTase-producing strain Alkalihalobacillus oshimensis CGMCC 23164 was isolated from Stevia planting soil. Using mass spectrometry-based secretome profiling, a high-efficiency CGTase that converted steviol glycosides to glucosylated steviol glycosides was identified and termed CGTase-13. CGTase-13 demonstrated optimal transglycosylation activity with 10 g/L steviol glycoside and 50 g/L soluble starch as substrates at <40 °C. Under the above conditions, the conversion rate of stevioside and rebaudioside A, two main components of steviol glycosides, reached 86.1% and 90.8%, respectively. To the best of our knowledge, this is the highest conversion rate reported to date. Compared with Toruzyme® 3.0 L, the commonly used commercial enzyme blends, glucosylated steviol glycosides produced using CGTase-13 exhibited weaker astringency and unpleasant taste, faster sweetness onset, and stronger sweetness intensity. Thus, CGTase provides a novel option for producing high-quality glucosylated steviol glycoside products and has great potential for industrial applications.

Alterations of gut and oral microbiota in the individuals consuming take-away food in disposable plastic containers.

Microplastics (MP) and nanoplastics (NP) exist in the disposable plastic take-away containers. This study aims to determine the gut and oral microbiota alterations in the individuals frequently and occasionally consuming take-away food in disposable plastic containers (TFDPC), and explore the effect of micro/nanoplastics (MNP) reduction on gut microbiota in mice. TFDPC consumption are associated with greater presences of gastrointestinal dysfunction and cough. Both occasional and frequent consumers have altered gut and oral microbiota, and their gut diversity and evenness are greater than those of non-TFDPC consuming cohort. Multiple gut and oral bacteria are associated with TFDPC consumers, among which intestinal Collinsella and oral Thiobacillus are most associated with the frequent consumers, while intestinal Faecalibacterium is most associated with the occasional consumers. Although some gut bacteria associated with the mice treated with 500 µg NP and 500 µg MP are decreased in the mice treated with 200 µg NP, the gut microbiota of the three MNP groups are all different from the control group. This study demonstrates that TFDPC induces gut and oral microbiota alterations in the consumers, and partial reduction of the size and amount of MNP cannot rectify the MNP-induced gut microbial dysbiosis.

Airborne polystyrene microplastics and nanoplastics induce nasal and lung microbial dysbiosis in mice.

Microplastics (MP) and nanoplastics (NP) have been found in multiple environments and creatures. However, their effects on the airway microbiota still remain poorly understood. In this study, a series of bioinformatic and statistical analyses were carried out to explore the influence of airborne MP and NP on the nasal and lung microbiota in mice. Both MP and NP were capable of inducing nasal microbial dysbiosis, and MP had a stronger influence on the lung microbiota than NP. Multiple nasal and lung bacteria were associated with MP and NP groups, among which nasal Staphylococcus and lung Roseburia were most associated with MP group, while nasal Prevotella and lung unclassified_Muribaculaceae were most associated with NP group. The nasal Staphylococcus, lung Roseburia, lung Eggerthella and lung Corynebacterium were associated with both MP and NP groups, which were potential biomarkers of micro/nanoplastics-induced airway dysbiosis. SAR11_Clade_Ia and SAR11_Clade_II were associated with both nasal and lung microbiota in MP group, while no such bacterium was determined in NP group. The relevant results suggest that both airborne MP and NP could induce nasal and lung microbial dysbiosis, and the relevant preventative and curable strategies deserve further investigations.

Characteristics of the intestinal bacterial microbiota profiles in Bifidobacterium pseudocatenulatum LI09 pre-treated rats with D-galactosamine-induced liver injury.

Bifidobacterium pseudocatenulatum LI09 could prevent D-galactosamine-induced liver injury. Our previous study has preliminarily determined that different intestinal microbiota profiles existed in the LI09-treated rats. Due to the sample size limitation, some subsequent analyses could not be achieved. In the current study, we conducted different experiments and bioinformatic analyses to characterise the distinct intestinal bacterial microbiota profiles in the LI09-treated rats with liver injury (i.e., LI09 group). Partition around medoids clustering analysis determined two intestinal microbiota profiles (i.e., Cluster_1_LI09 and Cluster_2_LI09) in LI09 group. Compared with Cluster_2_LI09, Cluster_1_LI09 group was determined at less dysbiotic microbial status and with lower level of liver injury. The two microbiota profiles were determined with distinct representative amplicon sequence variants (ASVs), among which, ASV1_Akkermansia and ASV3_Bacteroides were most associated with Cluster_1_LI09 and Cluster_2_LI09, respectively. Multiple representative phylotypes in Cluster_1_LI09 negatively correlating with liver function variables were assigned to Parabacteroides, suggesting Parabacteroides could benefit LI09 on modulating the liver function. In addition, ASV310_Lachnospiraceae, ASV501_Muribaculaceae and ASV484_Lachnospiraceae were determined as network gatekeepers in Cluster_1_LI09 network. The relevant results suggest that some intestinal bacteria could assist LI09 in lowering the intestinal microbial dysbiosis in the rats with liver injury, and their clinical application deserves further investigation.

Structural Color Controllable Humidity Response Chiral Nematic Cellulose Nanocrystalline Film.

Through self-assembly, environmentally friendly cellulose nanocrystals (CNCs) can form films with a photonic crystal structure whose pitch size can be adjusted in a variety of ways at the fabrication stage. Moreover, the films exhibit response performance to multiple stimuli, which offers extensive applications. Poly(ethylene glycol) (PEG) and CNCs combine to form a smaller chiral nematic domain that develops a solid film with a uniform spiral structure when slowly dried. By changing the composition of CNCs and PEG, flexible and flat photonic composite films with uniform structural colors from blue to red are prepared. Benefiting from the change in pitch size by insertion and detachment of water molecules into the chiral nematic structure, CNCs films and CNC-PEG composite films exhibit a reversible structural color change in response to different humidity. In addition, the chiral nematic films formed by the combination of glycerol and CNCs have a reversible stimulation response to hydrochloric acid gas. Similarly, adjusting the ratio of glycerol can control the pitch size of the films and, thus, the reflective color. In summary, the pitch size of the photonic crystal structure of the films can be precisely tuned by regulating the additive ratio, and the two prepared films have reversible responses to humidity and hydrochloric acid gas, respectively. The CNC-based films show promise in the application of colorimetric biosensors.

Deletion of NGG1 in a recombinant Saccharomyces cerevisiae improved xylose utilization and affected transcription of genes related to amino acid metabolism.

Production of biofuels and biochemicals from xylose using yeast cell factory is of great interest for lignocellulosic biorefinery. Our previous studies revealed that a natural yeast isolate Saccharomyces cerevisiae YB-2625 has superior xylose-fermenting ability. Through integrative omics analysis, NGG1, which encodes a transcription regulator as well as a subunit of chromatin modifying histone acetyltransferase complexes was revealed to regulate xylose metabolism. Deletion of NGG1 in S. cerevisiae YRH396h, which is the haploid version of the recombinant yeast using S. cerevisiae YB-2625 as the host strain, improved xylose consumption by 28.6%. Comparative transcriptome analysis revealed that NGG1 deletion down-regulated genes related to mitochondrial function, TCA cycle, ATP biosynthesis, respiration, as well as NADH generation. In addition, the NGG1 deletion mutant also showed transcriptional changes in amino acid biosynthesis genes. Further analysis of intracellular amino acid content confirmed the effect of NGG1 on amino acid accumulation during xylose utilization. Our results indicated that NGG1 is one of the core nodes for coordinated regulation of carbon and nitrogen metabolism in the recombinant S. cerevisiae. This work reveals novel function of Ngg1p in yeast metabolism and provides basis for developing robust yeast strains to produce ethanol and biochemicals using lignocellulosic biomass.

Characterising the Intestinal Bacterial and Fungal Microbiome Associated With Different Cytokine Profiles in Two Bifidobacterium strains Pre-Treated Rats With D-Galactosamine-Induced Liver Injury.

Multiple probiotics have protective effects against different types of liver injury. Different intestinal microbes could be beneficial to the protective effects of the probiotics on the treated cohorts in different aspects. The current study was designed to determine the intestinal bacterial and fungal microbiome associated with different cytokine profiles in the Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 pretreated rats with D-galactosamine-induced liver injury. In this study, partition around medoids clustering analysis determined two distinct cytokine profiles (i.e., CP1 and CP2) comprising the same 11 cytokines but with different levels among the LI09, LI10, positive control (PC), and negative control (NC) cohorts. All rats in PC and NC cohorts were determined with CP1 and CP2, respectively, while the rats with CP1 in LI09 and LI10 cohorts had more severe liver injury than those with CP2, suggesting that CP2 represented better immune status and was the "better cytokine profile" in this study. PERMANOVA analyses showed that the compositions of both bacterial and fungal microbiome were different in the LI10 cohorts with different cytokine profiles, while the same compositions were similar between LI09 cohorts with different cytokine profiles. The phylotype abundances of both bacteria and fungi were different in the rats with different cytokine profiles in LI09 or LI10 cohorts according to similarity percentage (SIMPER) analyses results. At the composition level, multiple microbes were associated with different cytokine profiles in LI09 or LI10 cohorts, among which Flavonifractor and Penicillium were the bacterium and fungus most associated with LI09 cohort with CP2, while Parabacteroides and Aspergillus were the bacterium and fungus most associated with LI10 cohort with CP2. These microbes were determined to influence the cytokine profiles of the corresponding cohorts. At the structure level, Corynebacterium and Cephalotrichiella were determined as the two most powerful gatekeepers in the microbiome networks of LI09 cohort CP2, while Pseudoflavonifractor was the most powerful gatekeeper in LI10 cohort with CP2. These identified intestinal microbes were likely to be beneficial to the effect of probiotic Bifidobacterium on the immunity improvement of the treated cohorts, and they could be potential microbial biomarkers assisting with the evaluation of immune status of probiotics-treated cohorts.

Preoperative Opioid Use and Readmissions Following Surgery.

OBJECTIVE: To assess the association between preoperative opioid exposure and readmissions following common surgery. SUMMARY BACKGROUND DATA: Preoperative opioid use is common, but its effect on opioid-related, pain-related, respiratory-related, and all-cause readmissions following surgery is unknown. METHODS: We analyzed claims data from a 20% national Medicare sample of patients ages ≥ 65 with Medicare Part D claims undergoing surgery between January 1, 2009 and November 30, 2016. We grouped patients by the dose, duration, recency, and continuity of preoperative opioid prescription fills. We used logistic regression to examine the association between prior opioid exposure and 30-day readmissions, adjusted for patient risk factors and procedure type. RESULTS: Of 373,991 patients, 168,579 (45%) filled a preoperative opioid prescription within 12 months of surgery, ranging from minimal to chronic high use. Preoperative opioid exposure was associated with higher rate of opioid-related readmissions, compared with naive patients [low: aOR=1.63, 95% CI=1.26-2.12; high: aOR=3.70, 95% CI=2.71-5.04]. Preoperative opioid exposure was also associated with higher risk of pain-related readmissions [low: aOR=1.27, 95% CI=1.23-1.32; high: aOR=1.62, 95% CI=1.53-1.71] and respiratory-related readmissions [low: aOR=1.10, 95% CI=1.05-1.16; high: aOR=1.44, 95% CI=1.34-1.55]. Low, moderate, and high chronic preoperative opioid exposures were predictive of all-cause readmissions (low: OR 1.09, 95% CI: 1.06-1.12); high: OR 1.23, 95% CI: 1.18-1.29). CONCLUSIONS: Higher levels of preoperative opioid exposure are associated with increased risk of readmissions after surgery. These findings emphasize the importance of screening patients for preoperative opioid exposure and creating risk mitigation strategies for patients.

Prenatal diagnosis and multidisciplinary management: a case report of congenital granular cell epulis and literature review.

Congenital granular cell epulis (CGCE) is a rare benign soft tissue lesion that usually originates from the neonatal gingiva and can lead to difficulty in breathing and feeding upon birth. This current case report describes a female newborn with a gingival mass that was identified by prenatal fetal ultrasonography. At birth, the oral mass was observed to protrude from the mouth, which adversely affected feeding. The lips could not be closed. The breathing was unaffected. Through a multidisciplinary team approach involving several healthcare professionals, the mass was successfully removed under general anaesthesia during an uncomplicated surgical procedure. Postoperative histopathological examination confirmed that the mass was a CGCE of the newborn. The infant recovered well after the operation.

Corrigendum to "Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus".

[This corrects the article DOI: 10.1155/2021/6632266.].

Correction: Factors Influencing Patients' Initial Decisions Regarding Telepsychiatry Participation During the COVID-19 Pandemic: Telephone-Based Survey.

[This corrects the article DOI: 10.2196/25469.].

Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus.

In recent years, the relationship between intestinal microbiota (IM) and the pathogenesis of type 2 diabetes mellitus (T2DM) has attracted much attention. The beneficial effects of IM on the metabolic phenotype of the host are often considered to be mediated by short-chain fatty acids (SCFAs), mainly acetate, butyrate, and propionate, the small-molecule metabolites derived from microbial fermentation of indigestible carbohydrates. SCFAs not only have an essential role in intestinal health but might also enter the systemic circulation as signaling molecules affecting the host's metabolism. In this review, we summarize the effects of SCFAs on glucose homeostasis and energy homeostasis and the mechanism through which SCFAs regulate the function of metabolically active organs (brain, liver, adipose tissue, skeletal muscle, and pancreas) and discuss the potential role of modulation of SCFAs as a therapeutic method for T2DM.

Factors Influencing Patients' Initial Decisions Regarding Telepsychiatry Participation During the COVID-19 Pandemic: Telephone-Based Survey.

BACKGROUND: Telepsychiatry enables patients to establish or maintain psychiatric care during the COVID-19 pandemic. Little is known about the factors influencing patients' initial decisions to participate in telepsychiatry in the midst of a public health crisis. OBJECTIVE: This paper seeks to examine factors influencing patients' initial decisions to accept or decline telepsychiatry immediately after the stay-at-home order in Michigan, their initial choice of virtual care modality (video or telephone), and their anticipated participation in telepsychiatry once clinics reopen for in-person visits. METHODS: Between June and August 2020, we conducted a telephone-based survey using a questionnaire comprising 14 quantitative and two qualitative items as part of a quality improvement initiative. We targeted patients who had an in-person appointment date that fell in the first few weeks following the Michigan governor's stay-at-home order, necessitating conversion to virtual visits or deferment of in-person care. We used descriptive statistics to report individual survey responses and assess the association between chosen visit type and patient characteristics and future participation in telepsychiatry using multivariable logistic regression. RESULTS: A total of 244 patients whose original in-person appointments were scheduled within the first 3 weeks of the stay-at-home order in Michigan completed the telephone survey. The majority of the 244 respondents (n=202, 82.8%) initially chose to receive psychiatric care through video visits, while 13.5% (n=33) chose telephone visits and 1.2% (n=3) decided to postpone care until in-person visit availability. Patient age correlated with chosen visit type (P<.001; 95% CI 0.02-0.06). Patients aged ≥44 years were more likely than patients aged 0-44 years to opt for telephone visits (relative risk reduction [RRR] 1.2; 95% CI 1.06-1.35). Patient sex (P=.99), race (P=.06), type of insurance (P=.08), and number of previous visits to the clinic (P=.63) were not statistically relevant. Half of the respondents (132/244, 54.1%) stated they were likely to continue with telepsychiatry even after in-person visits were made available. Telephone visit users were less likely than video visit users to anticipate future participation in telepsychiatry (RRR 1.08; 95% CI 0.97-1.2). Overall, virtual visits met or exceeded expectations for the majority of users. CONCLUSIONS: In this cohort, patient age correlates with the choice of virtual visit type, with older adults more likely to choose telephone visits over video visits. Understanding challenges to patient-facing technologies can help advance health equity and guide best practices for engaging patients and families through telehealth.

Design, Evolution, and Characterization of a Xylose Biosensor in Escherichia coli Using the XylR/xylO System with an Expanded Operating Range.

Genetically encoded biosensors are extensively utilized in synthetic biology and metabolic engineering. However, reported xylose biosensors are far too sensitive with a limited operating range to be useful for most sensing applications. In this study, we describe directed evolution of Escherichia coli XylR, and construction of biosensors based on XylR and the corresponding operator xylO. The operating range of biosensors containing the mutant XylR was increased by nearly 10-fold comparing with the control. Two individual amino acid mutations (either L73P or N220T) in XylR were sufficient to extend the linear response range to upward of 10 g/L xylose. The evolved biosensors described here are well suited for developing whole-cell biosensors for detecting varying xylose concentrations across an expanded range. As an alternative use of this system, we also demonstrate the utility of XylR and xylO as a xylose inducible system to enable graded gene expression through testing with ß-galactosidase gene and the lycopene synthetic pathway. This evolution strategy identified a less-sensitive biosensor for real applications, thus providing new insights into strategies for expanding operating ranges of other biosensors for synthetic biology applications.

Characteristics of three microbial colonization states in the duodenum of the cirrhotic patients.

Aim: Investigation of characteristics of different duodenal microbial colonization states in patients with liver cirrhosis (LC). Materials & methods: Deep-sequencing analyses of the 16S rRNA gene V1-V3 regions were performed. Results: Both bacterial compositions and richness were different between the three-clustered LC microbiotas, in other words, Cluster_1_LC, Cluster_2_LC and Cluster_3_LC. Cluster_1_LC were more likely at severe dysbiosis status due to its lowest modified cirrhosis dysbiosis ratio. OTU12_Prevotella and OTU10_Comamonas were most associated with Cluster_1_LC and Cluster_3_LC, respectively, while OTU38_Alloprevotella was vital in Cluster_2_LC. Pyruvate-ferredoxin/flavodoxin oxidoreductase, dihydroorotate dehydrogenase and branched-chain amino acid transport system substrate-binding protein were most associated with Cluster_1_LC, Cluster_2_LC and Cluster_3_LC, respectively. Conclusion: The three duodenal microbial colonization states had distinct representative characteristics, which might reflect the health status of cirrhotic patients.

The Neurospora RNA polymerase II kinase CTK negatively regulates catalase expression in a chromatin context-dependent manner.

Clearance and adaptation to reactive oxygen species (ROS) are crucial for cell survival. As in other eukaryotes, the Neurospora catalases are the main enzymes responsible for ROS clearance and their expression are tightly regulated by the growth and environmental conditions. The RNA polymerase II carboxyl terminal domain (RNAPII CTD) kinase complex (CTK complex) is known as a positive elongation factor for many inducible genes by releasing paused RNAPII near the transcription start site and promoting transcription elongation. However, here we show that deletion of CTK complex components in Neurospora led to high CAT-3 expression level and resistance to H2 O2 -induced ROS stress. The catalytic activity of CTK-1 is required for such a response. On the other hand, CTK-1 overexpression led to decreased expression of CAT-3. ChIP assays shows that CTK-1 phosphorylates the RNAPII CTD at Ser2 residues in the cat-3 ORF region during transcription elongation and deletion of CTK-1 led to dramatic decreases of SET-2 recruitment and H3K36me3 modification. As a result, histones at the cat-3 locus become hyperacetylated to promote its transcription. Together, these results demonstrate that the CTK complex is negative regulator of cat-3 expression by affecting its chromatin structure.

The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside.

Tacrolimus (TAC), the mainstay of maintenance immunosuppressive agents, plays a crucial role in new-onset diabetes after transplant (NODAT). Previous studies investigating the diabetogenic effects of TAC have focused on the ß cells of islets. In this study, we found that TAC contributed to NODAT through directly affecting hepatic metabolic homeostasis. In mice, TAC-induced hypoglycemia rather than hyperglycemia during starvation via suppressing gluconeogenetic genes, suggesting the limitation of fasting blood glucose in the diagnosis of NODAT. In addition, TAC caused hepatic insulin resistance and triglyceride accumulation through insulin receptor substrate (IRS)2/AKT and sterol regulatory element binding protein (SREBP1) signaling, respectively. Furthermore, we found a pivotal role of CREB-regulated transcription coactivator 2 (CRTC2) in TAC-induced metabolic disorders. The restoration of hepatic CRTC2 alleviated the metabolic disorders through its downstream molecules (eg, PCK1, IRS2, and SREBP1). Consistent with the findings from bench, low CRTC2 expression in graft hepatocytes was an independent risk factor for NODAT (odds ratio = 2.692, P = .023, n = 135). Integrating grafts' CRTC2 score into the clinical model could significantly increase the predictive capacity (areas under the receiver operating characteristic curve: 0.71 vs 0.79, P = .048). Taken together, in addition to its impact on pancreatic cells, TAC induces "hematogenous diabetes" via CRTC2 signaling. Liver-targeted management may be of help to prevent or heal TAC-associated diabetes.