A TrmBL2-like transcription factor mediates the growth phase-dependent expression of halolysin SptA in a concentration-dependent manner in Natrinema gari J7-2.

To cope with a high-salinity environment, haloarchaea generally employ the twin-arginine translocation (Tat) pathway to transport secretory proteins across the cytoplasm membrane in a folded state, including Tat-dependent extracellular subtilases (halolysins) capable of autocatalytic activation. Some halolysins, such as SptA of Natrinema gari J7-2, are produced at late-log phase to prevent premature enzyme activation and proteolytic damage of cellular proteins in haloarchaea; however, the regulation mechanism for growth phase-dependent expression of halolysins remains largely unknown. In this study, a DNA-protein pull-down assay was performed to identify the proteins binding to the 5'-flanking sequence of sptA encoding halolysin SptA in strain J7-2, revealing a TrmBL2-like transcription factor (NgTrmBL2). The ΔtrmBL2 mutant of strain J7-2 showed a sharp decrease in the production of SptA, suggesting that NgTrmBL2 positively regulates sptA expression. The purified recombinant NgTrmBL2 mainly existed as a dimer although monomeric and higher-order oligomeric forms were detected by native-PAGE analysis. The results of electrophoretic mobility shift assays (EMSAs) showed that NgTrmBL2 binds to the 5'-flanking sequence of sptA in a non-specific and concentration-dependent manner and exhibits an increased DNA-binding affinity with the increase in KCl concentration. Moreover, we found that a distal cis-regulatory element embedded in the neighboring upstream gene negatively regulates trmBL2 expression and thus participates in the growth phase-dependent biosynthesis of halolysin SptA. IMPORTANCE: Extracellular proteases play important roles in nutrient metabolism, processing of functional proteins, and antagonism of haloarchaea, but no transcription factor involved in regulating the expression of haloaechaeal extracellular protease has been reported yet. Here we report that a TrmBL2-like transcription factor (NgTrmBL2) mediates the growth phase-dependent expression of an extracellular protease, halolysin SptA, of haloarchaeon Natrinema gari J7-2. In contrast to its hyperthermophilic archaeal homologs, which are generally considered to be global transcription repressors, NgTrmBL2 functions as a positive regulator for sptA expression. This study provides new clues about the transcriptional regulation mechanism of extracellular protease in haloarchaea and the functional diversity of archaeal TrmBL2.

High-sensitivity C-reactive protein predicts microalbuminuria progression in essential hypertensive patients: a 3-year follow-up study.

OBJECTIVES: To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period. METHODS AND RESULTS: Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ±â€…9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group (n = 99, 50%), the group with baseline hs-CRP above the median (n = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) (P = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes (ß = 0.342; P < 0.001), baseline SBP (ß = 0.148; P = 0.02), and baseline log-transformed hs-CRP (ß = 0.169; P = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) (ß = -0.163; P = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes (ß = 0.359; P < 0.001) and baseline log-transformed hs-CRP (ß = 0.190; P = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups. CONCLUSION: Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria.

Mechanism Switch in Surface-Enhanced Raman Scattering: The Role of Nanoparticle Dimensions.

Surface-enhanced Raman scattering (SERS) is renowned for amplifying Raman signals, with electromagnetic mechanism (EM) enhancement arising from localized surface plasmon resonances and chemical mechanism (CM) enhancement as a result of charge transfer interactions. Despite the conventional emphasis on EM as a result of plasmonic effects, recent findings highlight the significance of CM when noble metals appear as smaller entities. However, the threshold size of the noble metal clusters/particles corresponding to the switch in SERS mechanisms is not clear at present. In this work, the VSe2-xOx/Au composites with different Au sizes are employed, in which a clear view of the SERS mechanism switch is observed at the Au size range of 16-21 nm. Our findings not only provide insight into the impact of noble metal size on SERS efficiency but also offer quantitative data to assist researchers in making informed judgments when analyzing SERS mechanisms.

High Serum Allergen-Specific IgE of House Dust Mite in Predicting the Risk of Comorbidity in Children with Allergic Conjunctivitis.

Purpose: To investigate the patterns of allergens in allergic conjunctivitis (AC) and the association with allergic comorbidity. Methods: This retrospective cross-sectional study enrolled 2972 children with AC. Clinical data, including sex, age, allergic comorbidities (allergic asthma, allergic rhinitis, and atopic dermatitis), and serum allergen-specific immunoglobulin E (sIgE), were collected from the electronic medical record (EMR). The categorical variables were compared with the chi-square test. The characteristics of allergens in children of different ages and comorbidities were analyzed by trend chi-square. The sensitivity level of HDM associated with AC and comorbidities was assessed by odds ratios (ORs) with 95% confidence intervals of logistic regression analysis. Results: A total of 2972 children (2015 boys and 957 girls) with AC were included in the study. The mean age was 3.78 (0.5~12) years. The most common allergen was house dust mite(HDM) (43.41%). With age, the positive rate for inhaled allergens gradually increased, and the positive rate for ingested allergens decreased. With the number of comorbidities increasing, the positive rates of sensitization were 38.33%, 74.51%, 80.72%, and 89.05%, and the incidence of polysensitization was 44.66%, 56.48%, 59.54%, and 74.59%, respectively. With the increase of HDM-sIgE level, the number of comorbidities and the risk increased gradually. Conclusion: HDM is the most common allergen in AC children of different ages. High levels of HDM-sIgE may be a predictor for allergic comorbidities. Children with polysensitization and high levels of HDM sIgE will be an important target population for future intervention in other allergy-related disease prevention.

Flipped Classroom Based on Outcomes-Based Education Improves Student Engagement and Clinical Analysis Competence in Undergraduates Ophthalmology Clerkship.

Objective: To investigate the effectiveness of flipped classrooms (FC) based on outcomes-based education (OBE) on clinical ophthalmology clerkships. Methods: Ninety-nine undergraduates were non-randomly assigned to the FC based on the OBE (FC-OBE) group or traditional lecture (TL) group in the ophthalmology clerkship. Pre- and post-tests were performed to assess student learning outcomes. Anonymous questionnaires were collected to compare students' attitudes and classroom engagements between the two groups. Results: More participants agreed FC-OBE was helpful in developing teamwork ability and knowing the work standard. Teaching staff in the FC-OBE classroom received higher evaluations. More participants in the FC-OBE group had higher classroom engagement in skills and emotions than in the TL group. The post-class test scores, mainly case analysis scores were higher in the FC-OBE group than in the TL group. Conclusion: FC-OBE classroom improves student engagement and clinical analysis competence in undergraduate ophthalmology clerkship.

LC/MS-guided isolation and GNPS procedures to identify flavonoid of HCoV-OC43 inhibitors.

The screening of based target compounds supported by LC/MS, MS/MS and Global Natural Products Social (GNPS) used to identify the compounds 1-10 of Butea monsperma. They were evaluated in human malignant embryonic rhabdomyoma cells (RD cells) infected with Human coronavirus OC43 (HCoV-OC43) and showed significant inhibitory activity. Target inhibition tests showed that compounds 6 and 8 inhibited the proteolytic enzyme 3CLpro, which is widely present in coronavirus and plays an important role in the replication process, with an effective IC50 value. The study confirmed that dioxymethylene of compound 8 may be a key active fragment in inhibiting coronavirus (EC50 7.2 µM, SI > 139.1). The results have led to identifying natural bioactive compounds for possible inhibiting HCoV-OC43 and developing drug for Traditional Chinese Medicine (TCM).

Stellate ganglion block for visceral pain in elderly patients undergoing video-assisted thoracoscopic lung cancer surgery: a randomized, controlled trial.

BACKGROUND: Visceral pain occurs commonly following thoracic surgery, but an effective method to relieve visceral pain in thoracic surgery remains controversial. We test the effect of stellate ganglion blocks (SGB) on perioperative visceral pain following video-assisted thoracoscopic surgery (VATS). METHODS: A prospective, randomized, controlled trial enrolled 77 elderly patients undergoing VATS. Patients were randomized to SGB followed by modified intercostal nerve block (Group S, n=37); or modified intercostal nerve block only (Group C, n=40). Remifentanil 0.02-0.2 µg·kg-1·min-1 was titrated to keep pain threshold index values between 40-65 and maintain mean arterial pressure or heart rate values around 20% of baseline values. Patient-controlled intravenous analgesia with sufentanil was used in the postoperative period. The co-primary outcomes were the perioperative cumulative opioid consumption and pain scores on movement at 24 h after surgery. RESULTS: Compared with control group, SGB greatly reduced the intraoperative remifentanil consumption[300.00(235.00-450.00)µg versus 710.00(500.00-915.00)µg; P<0.01], with no difference in cumulative sufentanil consumption to 48h post-surgery. There was a statistically significant difference in pain scores on movement at 24h between groups [4.00(3.00-4.00) versus 4.00(3.25-5.00); P=0.01]. Further exploratory analyses showed significant difference for intra-chest pain on movement at 24h [3.00(2.00-3.00) versus 3.00(2.25-4.00); P=0.01]. No significant difference was observed in nausea/vomiting, time to pass flatus and postoperative length of stay. CONCLUSION: Preoperative stellate ganglion blocks for elderly patients could effectively blunt intraoperative visceral stress and reduce postoperative visceral pain extending 24 h after VATS. This initial finding deserve further investigation.

[Characterization of carbon and oxygen isotopes of plant on climate and plant physiology at the southeastern margin of Qinghai-Tibet Plateau, China]. / é’è—é«˜åŽŸä¸œå—ç¼˜æ¤ç‰©ç¢³æ°§åŒä½ç´ å¯¹æ°”å€™åŠæ¤ç‰©ç”Ÿç†çš„è¡¨å¾.

To investigate the correlation between carbon and oxygen isotope compositions of plant cellulose and climatic factors as well as plant physiological indices on the southeastern margin of the Qinghai-Tibet Plateau, we examined plant species in eight sampling sites with similar latitudes and different longitudes in this region. Through the characteristics of δ13C and δ18O values, fractionation values (Δ13C and Δ18O) in leaf cellulose, we discussed water use efficiency (WUE) and the environmental factors, the variation of carbon and oxygen isotopes in the southeastern margin of the Qinghai-Tibet Plateau with elevation and longitude, and revealed the indication degrees of isotopic signals to different environments and vegetation physiology. By using the semi-quantitative model of carbon and oxygen dual isotopes, we investigated the physiological adaptation mechanisms of plants to varying environmental conditions. The results demonstrated that both Δ13C and Δ18O of cellulose decreased with increasing elevation and longitude, and Δ13C was more influenced by longitude, while Δ18O was more susceptible to elevation variation. Additionally, Δ13C and Δ18O were significantly and positively correlated with temperature (TEM), precipitation (PRE), potential evapotranspiration (PET), and relative humidity (RH). PRE was the dominant meteorological factor driving the variation of Δ13C, while RH was the dominant meteorological factor influencing Δ18O variation. In contrast to Δ13C, WUE showed a stronger correlation with elevation than with longitude, which increased as elevation and longitude increased. According to the carbon-oxygen model, plant stomatal conductance (gs) and photosynthetic capacity (Amax) decreased with increasing precipitation and relative humidity, while the values increased with increasing elevation and longitude. The combined analysis of carbon and oxygen isotopes of organic matters would yield additional environmental and gas exchange information for studies on climate tracing and vegetation physiology studies on the southeastern margin of the Qinghai-Tibet Plateau.

Lysosome-Targeted and pH-Activatable Phototheranostics for NIR-II Fluorescence Imaging-Guided Nasopharyngeal Carcinoma Phototherapy.

Currently, clinical therapeutic strategies for nasopharyngeal carcinoma (NPC) confront insurmountable dilemmas in which surgical resection is incomplete and chemotherapy/radiotherapy has significant side effects. Phototherapy offers a maneuverable, effective, and noninvasive pattern for NPC therapy. Herein, we developed a lysosome-targeted and pH-responsive nanophototheranostic for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of NPC. A lysosome-targeted S-D-A-D-S-type NIR-II phototheranostic molecule (IRFEM) is encapsulated within the acid-sensitive amphiphilic DSPE-Hyd-PEG2k to form IRFEM@DHP nanoparticles (NPs). The prepared IRFEM@DHP exhibits a good accumulation in the acidic lysosomes for facilitating the release of IRFEM, which could disrupt lysosomal function by generating an amount of heat and ROS under laser irradiation. Moreover, the guidelines of NIR-II fluorescence enhance the accuracy of PTT/PDT for NPC and avoid damage to normal tissues. Remarkably, IRFEM@DHP enable efficient antitumor effects both in vitro and in vivo, opening up a new avenue for precise NPC theranostics.

PERK inhibitor (ISRIB) improves depression-like behavior by inhibitions of HPA-axis over-activation in mice exposed to chronic restraint stress.

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.

Antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: an updated systematic review and meta-analysis.

BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16,189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

Identifications of novel host cell factors that interact with the receptor-binding domain of the SARS-CoV-2 spike protein.

SARS-CoV-2 entry into host cells is facilitated by the interaction between the receptor-binding domain of its spike protein (CoV2-RBD) and host cell receptor, ACE2, promoting viral membrane fusion. The virus also uses endocytic pathways for entry, but the mediating host factors remain largely unknown. It is also unknown whether mutations in the RBD of SARS-CoV-2 variants promote interactions with additional host factors to promote viral entry. Here, we used the GST pull-down approach to identify novel surface-located host factors that bind to CoV2-RBD. One of these factors, SH3BP4, regulates internalization of CoV2-RBD in an ACE2-independent but integrin- and clathrin-dependent manner and mediates SARS-CoV-2 pseudovirus entry, suggesting that SH3BP4 promotes viral entry via the endocytic route. Many of the identified factors, including SH3BP4, ADAM9, and TMEM2, show stronger affinity to CoV2-RBD than to RBD of the less infective SARS-CoV, suggesting SARS-CoV-2-specific utilization. We also found factors preferentially binding to the RBD of the SARS-CoV-2 Delta variant, potentially enhancing its entry. These data identify the repertoire of host cell surface factors that function in the events leading to the entry of SARS-CoV-2.

Recent Advances in the Synthesis of Rosettacin.

Camptothecin and its analogues show important antitumor activity and have been used in clinical studies. However, hydrolysis of lactone in the E ring seriously attenuates the antitumor activity. To change this situation, aromathecin alkaloids are investigated in order to replace camptothecins. Potential antitumor activity has obtained more and more attention from organic and pharmaceutical chemists. As a member of the aromathecin alkaloids, rosettacin has been synthesized via different methods. This review summarizes recent advances in the synthesis of rosettacin.

Macrophorins H and L, two new HMG-conjugate macrophorins from rihzospheric Penicillium sp. NX-05-G-3.

Macrophorins H (4) and L (5), two rare HMG-conjugate macrophorins along with three known macrophorins (1-3), three DMOA-derived meroterpenoids (6-8) and two ergosterol derivates (9-10) were isolated from sterilized rice medium cultured Penicillium sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds 1 and 2 showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC50 values ranging from 17.6 to 32.8 µM.

Sc-Modified C3N4 Nanotubes for High-Capacity Hydrogen Storage: A Theoretical Prediction.

Utilizing hydrogen as a viable substitute for fossil fuels requires the exploration of hydrogen storage materials with high capacity, high quality, and effective reversibility at room temperature. In this study, the stability and capacity for hydrogen storage in the Sc-modified C3N4 nanotube are thoroughly examined through the application of density functional theory (DFT). Our finding indicates that a strong coupling between the Sc-3d orbitals and N-2p orbitals stabilizes the Sc-modified C3N4 nanotube at a high temperature (500 K), and the high migration barrier (5.10 eV) between adjacent Sc atoms prevents the creation of metal clusters. Particularly, it has been found that each Sc-modified C3N4 nanotube is capable of adsorbing up to nine H2 molecules, and the gravimetric hydrogen storage density is calculated to be 7.29 wt%. It reveals an average adsorption energy of -0.20 eV, with an estimated average desorption temperature of 258 K. This shows that a Sc-modified C3N4 nanotube can store hydrogen at low temperatures and harness it at room temperature, which will reduce energy consumption and protect the system from high desorption temperatures. Moreover, charge donation and reverse transfer from the Sc-3d orbital to the H-1s orbital suggest the presence of the Kubas effect between the Sc-modified C3N4 nanotube and H2 molecules. We draw the conclusion that a Sc-modified C3N4 nanotube exhibits exceptional potential as a stable and efficient hydrogen storage substrate.

A Chinese patent medicine's long-term efficacy on non-dialysis patients with CKD stages 3-5: a retrospective cohort study.

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

Charge-transfer-driven ultrasensitive SERS sensing in a two-dimensional titanium carbonitride MXene.

Two-dimensional (2D) MXenes stand out as promising platforms for surface-enhanced Raman scattering (SERS) sensing owing to their metallic feature, various compositions, high surface area, compatibility with functionalization, and ease of fabrication. In this work, we report a high-performance 2D titanium carbonitride (Ti3CN) MXene SERS substrate. We reveal that the abundant electronic density of states near the Fermi level of Ti3CN MXene boosts the efficiency of photo-induced charge transfer at the interface of Ti3CN/molecule, resulting in significant Raman enhancement. The SERS sensitivity of Ti3CN MXene is further promoted through a 2D morphology regulation and molecular enrichment strategies. Moreover, prohibited drugs are detectable on this substrate, presenting the potential of trace-amount analysis on Ti3CN MXene. This work provides a deep insight of the SERS mechanisms of Ti3CN MXene and broadens the practical application of transition metal carbonitride MXene SERS substrates.