Islets in the body are never flat: transitioning from two-dimensional (2D) monolayer culture to three-dimensional (3D) spheroid for better efficiency in the generation of functional hPSC-derived pancreatic ß cells in vitro.

Diabetes mellitus (DM), currently affecting more than 537 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from a defect in insulin secretion, action, or both due to the loss or dysfunction of pancreatic ß cells. Since cadaveric islet transplantation using Edmonton protocol has served as an effective intervention to restore normoglycaemia in T1D patients for months, stem cell-derived ß cells have been explored for cell replacement therapy for diabetes. Thus, great effort has been concentrated by scientists on developing in vitro differentiation protocols to realize the therapeutic potential of hPSC-derived ß cells. However, most of the 2D traditional monolayer culture could mainly generate insulin-producing ß cells with immature phenotype. In the body, pancreatic islets are 3D cell arrangements with complex cell-cell and cell-ECM interactions. Therefore, it is important to consider the spatial organization of the cell in the culture environment. More recently, 3D cell culture platforms have emerged as powerful tools with huge translational potential, particularly for stem cell research. 3D protocols provide a better model to recapitulate not only the in vivo morphology, but also the cell connectivity, polarity, and gene expression mimicking more physiologically the in vivo cell niche. Therefore, the 3D culture constitutes a more relevant model that may help to fill the gap between in vitro and in vivo models. Interestingly, most of the 2D planar methodologies that successfully generated functional hPSC-derived ß cells have switched to a 3D arrangement of cells from pancreatic progenitor stage either as suspension clusters or as aggregates, suggesting the effect of 3D on ß cell functionality. In this review we highlight the role of dimensionality (2D vs 3D) on the differentiation efficiency for generation of hPSC-derived insulin-producing ß cells in vitro. Consequently, how transitioning from 2D monolayer culture to 3D spheroid would provide a better model for an efficient generation of fully functional hPSC-derived ß cells mimicking in vivo islet niche for diabetes therapy or drug screening. Video Abstract.

Laparoscopic right hemicolectomy with 2D or 3D video system technology: systematic review and meta-analysis.

BACKGROUND: Standard laparoscopic colorectal surgery relies on 2D image systems in most centers. However, 3D vision has gained popularity and is used nowadays in a constantly rising number of units. Right hemicolectomy with intracorporeal anastomosis and lymph node dissection represents a surgical procedure that may benefit the most from 3D vision. The aim of the study was to summarize the available literature on the use of 2D vs. 3D video imaging in patients undergoing laparoscopic right hemicolectomy. METHODS: A comprehensive literature review was conducted including Medline/PubMed, Embase, and Scopus (PROSPERO registration number CRD 42022344764) through October 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The risk of bias was evaluated using the ROBINS-I tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines and GRADEpro to develop a summary of evidence tables. Random-effects meta-analyses were conducted. RESULTS: Five observational retrospective studies (496 patients, 275 2D and 216 3D) were included. One study was rated as having a critical risk of bias; the remaining had low to moderate risk. 2D laparoscopic right hemicolectomy patients showed longer anastomotic time in 3/3 studies (MD = 3.32; 95%CI, 1.58-5.05; p = 0.002) and an upward trend in operative time in 4/5 studies (MD = 9.98; 95%CI, -1.42, 21.37; p = 0.086) compared to 3D. The two image video systems had similar short-term outcomes, including the number of lymph nodes harvested (MD = -0.67; 95%CI, -2.47, 1.13; p = 0.47), morbidity (OR post-operative complications = 1.12; 95%CI, 0.71-1.77; p = 0.62), and length of stay (MD = 0.27; 95%CI, -0.59, 1.13; p = 0.9). CONCLUSIONS: 2D and 2D laparoscopic right hemicolectomy had similar complications rate, with a shorter anastomotic time along with a downward trend in overall operative time for 3D. Larger prospective randomized trials are awaited before definitive conclusions can be drawn.

Does 3D laparoscopic video technology affect long-term survival in right hemicolectomy for cancer compared to standard 2D? A propensity score study.

BACKGROUND: There are few studies focused on the short-term results of laparoscopic right hemicolectomy performed with 2D (two-dimension) or 3D (three-dimension) video technology and none on the oncologic effects. The aim of the study was to assess the long-term results of laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis using 3D or 2D video in patients with right colon cancer with at least three years of oncologic follow-up. METHODS: Data from patients undergoing laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis for cancer in an 11-year period (June 2008-June 2019) and ≥ 3 years of follow-up were prospectively collected. Surgical procedures were performed by two expert laparoscopic surgeons. RESULTS: 111 patients were included in the study: 56 (50.5%) in the 3D group and 55 (49.5%) in the 2D group. Tumor stage and number of lymph nodes harvested were similar. Overall and disease-free survival were not different in the two groups. Local recurrence occurred in none of the patients, and distant metachronous metastases were similar in the two groups. A propensity score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. CONCLUSIONS: Laparoscopic 3D technology allows similar oncological results as 2D vision in LRH with intracorporeal anastomosis. Larger prospective randomized studies might confirm these results in the long-term follow-up.

Vitamin D Binding Protein and Renal Injury in Acute Decompensated Heart Failure.

Background: Renal function in acute decompensated heart faiulre (ADHF) is a strong predictor of disease evolution and poor outcome. Current biomarkers for early diagnostic of renal injury in the setting of ADHF are still controversial, and their association to early pathological changes needs to be established. By applying a proteomic approach, we aimed to identify early changes in the differential urine protein signature associated with development of renal injury in patients hospitalised due to ADHF. Materials and Methods: Patients (71 [64-77] years old) admitted at the emergency room with ADHF and hospitalised were investigated (N = 64). Samples (urine/serum) were collected at hospital admission (day 0) and 72 h later (day 3). Differential serum proteome was analysed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight (MALDI-ToF/ToF). Validation studies were performed using ELISA. Results: Proteomic analysis depicted urinary vitamin D binding protein (uVDBP) as a two spots protein with increased intensity in ADHF and significant differences depending on the glomerular filtration rate (GFR). Urinary VDBP in patients with ADHF at hospitalisation was > threefold higher than in healthy subjects, with the highest levels in those patients with ADHF already presenting renal dysfunction. At day 3, urine VDBP levels in patients maintaining normal renal function dropped to normal values (P = 0.03 vs. day 0). In contrast, urine VDBP levels remained elevated in the group developing renal injury, with values twofold above the normal range (P < 0.05), while serum creatinine and GF levels were within the physiological range in this group. Urinary VDBP in ADHF positively correlated with markers of renal injury such as cystatin C and Kidney Injury Molecule 1 (KIM-1). By ROC analysis, urinary VDBP, when added to cystatin C and KIM-1, improved the prediction of renal injury in patients with ADHF. Conclusion: We showed increased urine VDBP in patients with ADHF at hospital admission and a differential uVDBP evolution pattern at early stage of renal dysfunction, before pathological worsening of GFR is evidenced.

Ultrasmall Au nanoparticles modified 2D metalloporphyrinic metal-organic framework nanosheets with high peroxidase-like activity for colorimetric detection of organophosphorus pesticides.

Ultrasmall Au nanoparticles (UsAuNPs) in the size range of 4.0-7.0 nm was successfully immobilized on the surface of 2D metalloporphyrinic metal-organic framework nanosheets (2D MOF). Firstly, The obtained hybrid nanomaterial, UsAuNPs/2D MOF, was fully characterized by TEM, HRTEM, element mapping images and XPS. Then, the peroxidase-like activity of UsAuNPs/2D MOF was comparatively studied with other hybrid nanozyme to explore the influence of AuNPs size on peroxidase-like activity. Further, UsAuNPs/2D MOF with outstanding peroxidase-like activity was selected to form ternary cascade enzyme reaction with acetylcholinesterase (AChE) and choline oxidase (ChOx). Based on the inhibitory effect of organophosphorus pesticides on AChE, a fast and sensitive colorimetric method was established for trichlorfon detection with the advantages of simple operation, low detection limit (1.7 µM), good linear range (1.7-42.4 µM) and high accuracy (recovery rate of 96.6-105.3%). Finally, this method was applied to visual analysis of trichlorfon concentration in tomatoes, cucumbers and eggplants.

Study of effects of anthracycline drugs on myocardial function in breast cancer patients by quantitative analysis of layer-specific strain via 2D-STI technology.

OBJECTIVE: This study aimed to explore the value of layer-specific strain analysis by two-dimensional speckle tracking imaging (2D-STI) in the assessment of myocardial toxicity in breast cancer patients receiving anthracycline chemotherapy. METHODS: Thirty-four breast cancer patients receiving anthracycline chemotherapy were prospectively enrolled. Conventional echocardiography and 2D-STI were evaluated at baseline after the third and sixth cycles of anthracycline chemotherapy. The strains of different layers of left ventricle (LV) including peak systolic longitudinal strain (endo-LS, mid-LS, epi-LS) and circumferential strain (endo-CS, mid-CS, epi-CS) were measured using EchoPAC analysis software. Peak systolic longitudinal strain (MV-LS, PM-LS, AP-LS), circumferential strain (MV-CS, PM-CS, AP-CS) and radial strain (MV-RS, PM-RS, AP-RS) were measured at mitral valve, papillary muscle and apex levels of LV respectively. Global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and left ventricular twist (LVtw) were also analyzed. RESULTS: There was no significant difference in the structural and functional parameters of conventional 2D echocardiography in different cycles of anthracycline chemotherapy (P>0.05); layer specific LS and CS in various cycles decreased layer by layer from inside to outside. LS and CS increased from basal segment to apical segment, while RS showed no obvious gradient characteristics; compared with baseline, GLS and LSs (endo-PM, endo-AP, mid-PM, mid-AP and epi-AP) of LV decreased significantly after the third cycle of chemotherapy (P<0.05); LSs (epi-MV and epi-AP) decreased significantly after the sixth cycle of chemotherapy (P<0.05). No significant changes were detected in layer specific CS, RS and LVtw (P>0.05). CONCLUSION: Layer-specific strain analysis by 2D-STI technology can quantitatively analyze global and regional functions of LV. The myocardial toxicity due to anthracycline chemotherapy can be detected by layer-specific LS of LV in early stage, which is great valuable to guiding clinical early intervention and improving prognosis.

Three-dimension versus two-dimension video-assisted thoracoscopic surgery for esophageal cancer: a meta-analysis.

BACKGROUND: It still remains unclear whether three-dimension (3D) video-assisted thoracoscopic surgery (VATS) for esophageal cancer is safe and reasonable. This meta-analysis aims at assessing the effectiveness and safety of 3D VATS for esophageal cancer in comparison with that of two-dimension (2D) VATS. METHODS: All the relevant data systematically analyzed in this thesis is from PubMed, Embase, The Cochrane Library, Web of Science and clinicaltrials.gov, and the time span for retrieval is from the date of the database establishment to February 2021. The research on the efficacy and safety of 3D VATS for esophageal cancer and 2D VATS is consistent with our meta-analysis. Continuous variables and dichotomy variables are compared using odds ratio, average or standard average differences with 95% confidence interval (95% CI), and P values, respectively. RESULTS: In five studies of this paper, there were 553 patients in total (3D VATS group, n=266 and 2D VATS group, n=287). Patients in the 3D group had shorter operation time [standardized mean difference (SMD) =-0.99, 95% CI: -1.66 to -0.32; P=0.004], and less bleeding (SMD =-0.88, 95% CI: -1.66 to -0.10; P=0.03) than those in the 2D group. The total amount of dissected lymph node and post-operative complications in the 2D group and the 3D group were nearly the same, showing no significant difference. DISCUSSION: The results of this meta-analysis showed that 3D VATS for esophageal cancer will be more applied and developed in the future. REGISTRATION NUMBER OF PROSPERO: CRD42021238863.

Cysteine-assisted photoelectrochemical immunoassay for the carcinoembryonic antigen by using an ITO electrode modified with C3N4-BiOCl semiconductor and CuO nanoparticles as antibody labels.

A sensitive photoelectrochemical (PEC) immunoassay for the carcinoembryonic antigen (CEA) is described that is based on the use of C3N4-BiOCl semiconductor on an ITO electrode. The photocurrent of the modified electrode was measured under visible light illumination. It increased in presence of L-cysteine due to rapid separation of the photoexcited electrons and holes. A sandwich-type immunoassay in a 96-well microtiter plate format used CuO nanoparticles as label for the secondary antibody. The Cu2+ is released from the CuO in the sandwich complex by treatment with acid. The free Cu2+ combined with both the cysteine and the electron receptors of C3N4 and BiOCl. Under optimal conditions, this dual action immensely decreases the photocurrent of the PEC system, and the response is inversely proportional to the CEA concentrations from 0.1 pg mL-1 to 10 ng mL-1 at the working voltage of 0 V (vs. SCE). The detection limit is 0.1 pg mL-1, and the method is exhibited satisfactory selective, repeatable and stable. Graphical abstract Schematic representation of an immunoassay based on cysteine-assisted C3N4-BiOCl photoelectrochemical platform. CuO nanoparticles were utilized as labels in immunocomplex to release Cu2+ in acidic condition. Carcinoembryonic antigen in sample was detected sensitively by dual function of Cu2+ with cysteine and C3N4-BiOCl semiconductor.

New insights on Ethambutol Targets in Mycobacterium tuberculosis.

BACKGROUND: In recent years, very few effective drugs against Mycobacterium tuberculosis have emerged, which motivates the research with drugs already used in the treatment of tuberculosis. Ethambutol is a bacteriostatic drug that affects cell wall integrity, but the effects of this drug on bacilli are not fully exploited. OBJECTIVE: Based on the need to better investigate the complex mechanism of action of ethambutol, our study presented the proteome profile of M. tuberculosis after different times of ethambutol exposure, aiming to comprehend the dynamics of bacilli response to its effects. M. tuberculosis was exposed to ½ MIC of ethambutol at 24 and 48 hours. The proteins were identified by MALDI-TOF/TOF. RESULTS: The main protein changes occurred in metabolic proteins as dihydrolipoyl dehydrogenase (Rv0462), glutamine synthetase1 (Rv2220), electron transfer flavoprotein subunit beta (Rv3029c) and adenosylhomocysteinase (Rv3248c). CONCLUSION: Considering the functions of these proteins, our results support that the intermediary metabolism and respiration were affected by ethambutol and this disturbance provided proteins that could be explored as additional targets for this drug.

Dye sensitized photoelectrochemical immunosensor for the tumor marker CEA by using a flower-like 3D architecture prepared from graphene oxide and MoS2.

The authors describe a dye-sensitized photoelectrochemical immunoassay for the tumor marker carcinoembryonic antigen (CEA). The method employs the rhodamine dye Rh123 with red color and absorption maximum at 500 nm for spectral sensitization, and a 3D nanocomposite prepared from graphene oxide and MoS2 acting as the photoelectric conversion layer. The nanocomposite with flower-like 3D architectures was characterized by transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, and UV-vis diffuse reflectometry. A photoelectrochemical sandwich immunoassay was developed that is based on the use of the nanocomposite and based on the specific binding of antibody and antigen, and by using a secondary antibody labeled with Rh123 and CdS (Ab2-Rh123@CdS). Under optimal conditions and at a typical working voltage of 0 V (vs. Hg/HgCl2), the photocurrent increases linearly 10 pg mL-1 to 80 ng mL-1 CEA concentration range, with a 3.2 pg mL-1 detection limit. Graphical abstract Flower-like GO-MoS2 complex with high efficiency of electron transport was synthesized to construct photoelectrochemical platform. The sandwich-type immunoassay was built on this platform based on specific binding of antigen and antibody. Carcinoembryonic antigen in sample was detected sensitively by using sensitization of rhodamine dye Rh123 as signal amplification strategy.

[Study on quality evaluation of Dihuang (Rehmannia glutinosa) by two-dimension HPLC fingerprints and chemometrics methods].

The study is to establish the two-dimension HPLC fingerprints of Dihuang (Rehmannia glutinosa), by HPLC-PDA and HPLC-ELSD methods. The separations were performed on Waters Atlantis®T3（4.6 mm× 250 mm，5 µm）and Welch Ultimate®Hilic-NH2（4.6 mm× 250 mm，5 µm）columns with the gradient elution of acetonitrile-0.01% phosphoric acid and acetonitrile-water, respectively. The chromatographic display wavelength for PDA detector was set at 203 nm. For HPLC-ELSD, the nebulizer was set as cooling mode, the drift tube temperature was set at 60 °C and the gas pressure was 35.0 psi. Based on similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine, 26 and 10 chromatographic peaks were determined as common components for HPLC-PDA and HPLC-ELSD fingerprints, respectively. Chemometrics analyses, such as similarity analysis; cluster analysis and principal component analysis, were performed on the common peak areas in two-dimension fingerprints for 41 batches of Dihuang from multiple sources. The results showed that the HPLC-PDA fingerprint could distinguish dried rehmannia root between different sources, and HPLC-ELSD fingerprint could differentiate dried rehmannia root from prepared rehmannia root. The two-dimension fingerprints were established with advantages of a good degree of separation, abundant chemical information and multi-components identified including two nucleosides (adenosine and uridine)，four iridoid glycosides (catalpa alcohol，rehmaionoside D，rehmaionoside A and leonuride)，two phenylethanoid glycosides (acteoside and cistanoside A) and nine sugars. The method is simple and practical, which could be used for the identification and quality assessment for Dihuang.

Poly[[(µ4-benzene-1,3,5-tri-carboxyl-ato-κ(4) O (1):O (1'):O (2):O (3))bis-(2,2-bi-pyridine-κ(2) N,N')(µ2-hydroxido)dicopper(II)] trihydrate].

In the title two-dimensional coordination polymer, {[Cu2(C9H3O6)(OH)(C10H8N2)2]·3H2O} n , each of the two independent Cu(II) atoms is coordinated by a bridging OH group, two O atoms from two benzene-1,3,5-tri-carboxyl-ate (L) ligands and two N atoms from a 2,2- bi-pyridine (bipy) ligand in a distorted square-pyramidal geometry. Each L ligand coordinates four Cu(II) atoms, thus forming a polymeric layer parallel to the bc plane with bipy molecules protruding up and down. The lattice water mol-ecules involved in O-H⋯· O hydrogen bonding are situated in the inner part of each layer. The crystal packing is consolidated by π-π inter-actions between the aromatic rings of bipy ligands from neigbouring layers [inter-centroid distance = 3.762 (3) Å].