Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

On the Question of Uncatalyzed CO Insertion into a Hydrazone Double Bond: A Comparative Study Using Different CO Sources and Substrates.

Because of endogenous signaling roles of carbon monoxide (CO) and its demonstrated pharmacological effects, there has been extensive interests in developing fluorescent CO probes. Palladium-mediated CO insertion has been successfully used for such applications. However, recent years have seen many publications of using uncatalyzed CO insertion into a hydrazone double bond as a way to sense CO. Such chemistry has no precedents otherwise. Further, the rigor of the CO-sensing work was largely based on using ruthenium-carbonyl complexes such as CORM-3 as CO surrogates, which have been reported to have extensive chemical reactivity and to release largely CO2 instead of CO unless in the presence of a strong nucleophile such as dithionite. For all of these, it is important to reassess the feasibility of such a CO-insertion reaction. By studying two of the reported "CO probes" using CO gas, this study finds no evidence of CO insertion into a hydrazone double bond. Further, the chemical reaction between CO gas and a series of eight hydrazone compounds was conducted, leading to the same conclusion. Such findings are consistent with the state-of-the-art knowledge of carbonylation chemistry and do not support uncatalyzed CO insertion as a mechanism for developing fluorescent CO probes.

Robotic natural orifice specimen extraction surgery versus robotic transabdominal specimen extraction surgery for early-stage rectal cancer: a multicenter propensity score-matched analysis (in China).

BACKGROUND: Despite the global increase in the adoption of robotic natural orifice specimen extraction surgery (R-NOSES), its advantages over robotic transabdominal specimen extraction surgery (R-TSES) for treating early-stage rectal cancer remain debated. There is scant nationwide, multicenter studies comparing the surgical quality and short-term outcomes between R-NOSES and R-TSES for this condition. OBJECTIVE: This retrospective cohort study was conducted nationally across multiple centers to compare the surgical quality and short-term outcomes between R-NOSES and R-TSES in early-stage rectal cancer. DESIGN: Multicenter retrospective cohort trial. SETTING: Eight experienced surgeons from 8 high-volume Chinese colorectal cancer treatment centers. PATIENTS: The study included 1086 patients who underwent R-NOSES or R-TSES from October 2015 to November 2023 at the 8 centers. Inclusion criteria were: (1) histologically confirmed rectal adenocarcinoma; (2) robotic total mesorectal excision; (3) postoperative pathological staging of TisN0M0 or T1-2N0M0; (4) availability of complete surgical and postoperative follow-up data. Patients were matched 1:1 in the R-NOSES and R-TSES groups using the propensity score matching (PSM) technique. RESULTS: After PSM, 318 matched pairs with well-balanced patient characteristics were identified. The operation time for the R-NOSES group was significantly longer than that for the R-TSES group [140 min (125-170 min) vs. 140 min (120-160 min), P = 0.032]. Conversely, the times to first flatus and initial oral intake in the R-NOSES group were significantly shorter than those in the R-TSES group [48 h (41-56 h) vs. 48 h (44-62 h), P = 0.049 and 77 h (72-94 h) vs. 82 h (72-96 h), P = 0.008], respectively. Additionally, the length of postoperative hospital stay was shorter in the R-NOSES group compared with the R-TSES group [7 day (7-9 day) vs. 8 day (7-9 day), P = 0.005]. The overall postoperative complication rates were similar between the groups (10.7% in the R-NOSES group vs. 11.9% in the R-TSES group, P = 0.617). However, the R-NOSES group had a lower incidence of wound complications compared to the R-TSES group (0.0% vs. 2.2%, P = 0.015). Regarding surgical stress response, the R-NOSES group showed superior outcomes. Additionally, patients in the R-NOSES group required fewer additional analgesics on postoperative days 1, 3, and 5 and reported lower pain scores compared to the R-TSES group. The body image scale (BIS) and cosmetic scale (CS) scores were also significantly higher in the R-NOSES group. Furthermore, the R-NOSES group demonstrated significantly better outcomes in functional dimensions such as physical, role, emotional, social, and cognitive functioning, and in symptoms like fatigue and pain, when compared to the R-TSES group. LIMITATIONS: It is imperative to ensure the safe and standardized implementation of R-NOSES through the establishment of a uniform training protocol. CONCLUSIONS: These results affirm that R-NOSES is a safe and effective treatment for early-stage rectal cancer when meticulously executed by skilled surgeons.

Sensing a CO-Releasing Molecule (CORM) Does Not Equate to Sensing CO: The Case of DPHP and CORM-3.

Carbon monoxide (CO) is an endogenous signaling molecule with demonstrated pharmacological effects. For studying CO biology, there is a need for sensitive and selective fluorescent probes for CO as research tools. In developing such probes, CO gas and/or commercially available metal-carbonyl-based "CO-releasing molecules" (CORMs) have been used as CO sources. However, new findings are steadily emerging that some of these commonly used CORMs do not release CO reliably in buffers commonly used for studying such CO probes and have very pronounced chemical reactivities of their own, which could lead to the erroneous identification of "CO probes" that merely detect the CORM used, not CO. This is especially true when the CO-sensing mechanism relies on chemistry that is not firmly established otherwise. Cu2+ can quench the fluorescence of an imine-based fluorophore, DPHP, presumably through complexation. The Cu2+-quenched fluorescence was restored through the addition of CORM-3, a Ru-based CORM. This approach was reported as a new "strategy for detecting carbon monoxide" with the proposed mechanism being dependent on CO reduction of Cu2+ to Cu1+ under near-physiological conditions ( Anal. Chem. 2022, 94, 11298-11306). The study only used CORM-3 as the source of CO. CORM-3 has been reported to have very pronounced redox reactivity and is known not to release CO in an aqueous solution unless in the presence of a strong nucleophile. To assess whether the fluorescent response of the DPHP-Cu(II) cocktail to CORM-3 was truly through detecting CO, we report experiments using both pure CO and CORM-3. We confirm the reported DPHP-Cu(II) response to CORM-3 but not pure CO gas. Further, we did not observe the stated selectivity of DPHP for CO over sulfide species. Along this line, we also found that a reducing agent such as ascorbate was able to induce the same fluorescent turn-on as CORM-3 did. As such, the DPHP-Cu(II) system is not a CO probe and cannot be used to study CO biology. Corollary to this finding, it is critical that future work in developing CO probes uses more than a chemically reactive "CO donor" as the CO source. Especially important will be to confirm the ability of the "CO probe" to detect CO using pure CO gas or another source of CO.

Comparison of robotic-assisted and laparoscopic-assisted natural orifice specimen extraction surgery in short-terms outcomes of middle rectal cancer.

BACKGROUND: Surgery is becoming less invasive as technology advances. Natural orifice specimen extraction surgery (NOSES) ushered in a new era of minimally invasive techniques. At the same time, NOSES is gaining popularity in the world. With their distinct advantages, surgical robots have advanced the development of NOSES. The aim of current study was to compare the short-term outcomes between robotic-assisted NOSES and laparoscopic-assisted NOSES for the treatment of middle rectal cancer. METHODS: Patients with middle rectal cancer who underwent robotic-assisted or laparoscopic-assisted NOSES at the First Affiliated Hospital of Nanchang University between January 2020 and June 2022 had their clinicopathological data collected retrospectively. 46 patients were enrolled in the study: 23 in the robotic group and 23 in the laparoscopic group. Short-term outcomes and postoperative anal function in the two groups were compared. RESULTS: There was no significant difference in the clinicopathological data between the two groups. The robotic group had less intraoperative blood loss (p = 0.04), less postoperative abdominal drainage (p = 0.02), lower postoperative white blood cell counts (p = 0.024) and C-reactive protein levels (p = 0.017), and shorter catheter removal time when compared to the laparoscopic group (p = 0.003). Furthermore, there were no significant difference in mean operative time (159 ± 31 min vs 172 ± 41 min) between the robotic and laparoscopic groups (p = 0.235), but time to naked the rectum (86.4 ± 20.9 min vs. 103.8 ± 31.5 min p = 0.033) and time of digestive tract reconstruction (15.6 ± 3.88 min vs. 22.1 ± 2.81 min p < 0.01) in the robotic group were significantly shorter than laparoscopic group. The robotic group had lower postoperative Wexner scores than the laparoscopic group. CONCLUSIONS: This research reveals that combining a robotic surgical system and NOSES results in superior outcomes, with short-term outcomes preferable to laparoscopic-assisted NOSES.

Comparison of short-term efficacy analysis of medium-rectal cancer surgery with robotic natural orifice specimen extraction and robotic transabdominal specimen extraction.

BACKGROUND: With the development of minimally invasive technology, the trauma caused by surgery get smaller, At the same time, the specimen extraction surgery through the natural orifice is more favored by experts domestically and abroad, robotic surgery has further promoted the development of specimen extraction surgery through the natural orifice. The aim of current study is to compare the short-term outcomes of robotic-assisted natural orifice specimen extraction (NOSES ) and transabdominal specimen extraction(TRSE ) in median rectal cancer surgery. METHODS: From January 2020 to January 2023, 87 patients who underwent the NOSES or TRSE at the First Affiliated Hospital of Nanchang University were included in the study, 4 patients were excluded due to liver metastasis. Of these, 50 patients were in the TRSE and 33 patients in the NOSES. Short-term efficacy was compared in the two groups. RESULTS: The NOSES group had less operation time (P < 0.001), faster recovery of gastrointestinal function (P < 0.001), shorter abdominal incisions (P < 0.001), lower pain scores(P < 0.001). lower Inflammatory indicators of the white blood cell count and C-reactive protein content at 1, 3, and 5 days after surgery (P < 0.001, P = 0.037). There were 9 complications in the NOSES group and 11 complications in the TRSE group(P = 0.583). However, there were no wound complications in the NOSES group. The number of postoperative hospital stays seems to be same in the two groups. And there was no significant difference in postoperative anus function (P = 0.591). CONCLUSIONS: This study shows that NOSES and TRSE can achieve similar radical treatment effects, NOSES is a feasible and safe way to take specimens for rectal cancer surgery in accordance with the indication for NOSES.

H2S Sensors: Synthesis, Optical Properties, and Selected Biomedical Applications under Visible and NIR Light.

Hydrogen sulfide (H2S) is an essential signaling gas within the cell, and its endogenous levels are correlated with various health diseases such as Alzheimer's disease, diabetes, Down's syndrome, and cardiovascular disease. Because it plays such diverse biological functions, being able to detect H2S quickly and accurately in vivo is an area of heightened scientific interest. Using probes that fluoresce in the near-infrared (NIR) region is an effective and convenient method of detecting H2S. This approach allows for compounds of high sensitivity and selectivity to be developed while minimizing cytotoxicity. Herein, we report a review on the synthesis, mechanisms, optical properties, and selected biomedical applications of H2S sensors.

Highly Sensitive Multifunctional Electronic Skin Based on Nanocellulose/MXene Composite Films with Good Electromagnetic Shielding Biocompatible Antibacterial Properties.

Electronic skin has aroused extensive research interest due to high similarity with human skin. Realizing a multifunctional electronic skin that is highly consistent with skin functions and endowed with more other functions is now a more urgent need and important challenge. Here, we use 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-oxidized cellulose nanofibril (TOCN) dispersion and highly conductive Ti3C2TX dispersion to prepare TOCN/Ti3C2TX composite film through vacuum-assisted filtration. The obtained composite film imitating the nacre-like lamellar structure of natural shells has good mechanical properties (124.6 MPa of tensile strength). Meanwhile, the composite film also showed excellent electromagnetic shielding performance (36 dB), biocompatibility, and antibacterial properties. In addition, the piezoresistive sensor assembled from the composite film exhibited a high sensitivity (11.6 kPa-1), fast response and recovery time (≤10 ms), ultralow monitoring limit (0.2 Pa), and long-term stability (>10 000 cycles). It also could detect human daily activities such as finger bent, chewing, and so on.

Surgical and oncological outcomes of robotic- versus laparoscopic-assisted distal gastrectomy with D2 lymphadenectomy for advanced gastric cancer: a propensity score­matched analysis of 1164 patients.

BACKGROUND: Studies on surgical outcomes after robotic surgery are increasing; however, long-term oncological results of studies comparing robotic-assisted distal gastrectomy (RADG) versus laparoscopic-assisted distal gastrectomy (LADG) for advanced gastric cancer (AGC) are still limited. This study aimed to assess the surgical and oncological outcomes of RADG and LADG for the treatment of AGC. METHODS: A total of 1164 consecutive AGC patients undergoing RADG or LADG were enrolled between January 2015 and October 2021. Propensity score-matched (PSM) analysis was performed to minimize selection bias. The perioperative and oncological outcomes between the two groups were compared. RESULTS: Patient's characteristics were comparable between the two groups after PSM. RADG group represented a longer operative time (205.2 ± 43.1 vs 185.3 ± 42.8 min, P < 0.001), less operative blood loss (139.3 ± 97.8 vs 167.3 ± 134.2 ml, P < 0.001), greater retrieved lymph nodes (LNs) number (31.4 ± 12.1 vs 29.4 ± 12.3, P = 0.015), more retrieved LNs in the supra-pancreatic areas (13.4 ± 5.0 vs 11.4 ± 5.1, P < 0.001), and higher medical costs (13,608 ± 4326 vs 10,925 ± US $3925, P < 0.001) than LADG group. The overall complication rate was 13.7% in the RADG group and 16.6% in the LADG group, respectively; the difference was not significantly different (P = 0.242). In the subgroup analysis, the benefits of RADG were more evident in high BMI patients. Moreover, the 3-year overall survival (75.5% vs 73.1%, P = 0.471) and 3-year disease-free survival (72.9% vs 71.4%, P = 0.763) were similar between the two groups. CONCLUSION: RADG appears to be a safe and feasible procedure and could serve as an alternative treatment for AGC in experienced centers.

Male urogenital function after robot-assisted and laparoscopic total mesorectal excision for rectal cancer: a prospective cohort study.

BACKGROUND: Urogenital dysfunction is recognized as a serious complication affecting patient quality of life after rectal cancer surgery to treat rectal cancer; however, the studies focus on the urogenital function after robot-assisted rectal cancer surgery compared to laparoscopic surgery are limited. METHODS: Male patients undergoing robotic total mesorectal excision (R-TME) or laparoscopic total mesorectal excision (L-TME) were prospectively enrolled. The International Prostate Symptom Score (IPSS) and the five-item version of the International Index of Erectile Function (IIEF-5) scale were used to compare the urogenital function of the two groups preoperatively and 3, 6, and 12 months postoperatively. RESULTS: Eighty-nine patients who planned to undergo R-TME and L-TME were prospectively enrolled; 77 patients of these patients (86.5%) completed all questionnaires at all time points and were thus included in the final analysis. Of the included patients, 38 underwent R-TME and 39 underwent L-TME. There was no significant difference in age, BMI, American Society of Anesthesiologists (ASA) score, tumor location, neoadjuvant therapy, operation method, postoperative pathological results and adjuvant therapy between the two groups. Preoperative urogenital function was similar in both groups; however, the IPSS was significantly lower in R-TME patients than that in T-TME patients at 6 months and 12 months [(7.82 ± 2.25 vs. 9.95 ± 3.01, P = 0.006; 7.62 ± 2.5 vs. 9.12 ± 2.64, P = 0.012)]. IIEF-5 scores decreased 3 months after R-TME and L-TME surgery (14.87 ± 3.27 vs. 13.92 ± 3.62, p = 0.231) and then gradually increased; at 12 months, IIEF-5 scores were comparable to those at baseline in both groups. IIEF-5 scores were higher in R-TME patients than those in L-TME patients at 6 months (18.55 ± 3.45 vs. 16.75 ± 3.26, P = 0.021), but there was no significant difference between the two groups at 12 months (21.22 ± 3.06 vs. 19.95 ± 3.03, P = 0.071). CONCLUSIONS: The robotic approach for TME was associated with more rapid restoration of male urogenital function than the laparoscopic approach.

Monitoring the Dynamics of Proteome Aggregation in Live Cells Using a Solubilized and Noncovalent Analogue of Fluorescent Protein Chromophores.

Stress-induced intracellular proteome aggregation is a hallmark and a biomarker of various human diseases. Current sensors requiring either cellular fixation or covalent modification of the entire proteome are not suitable for live-cell applications and dynamics study. Herein, we report a noncovalent, cell-permeable, and fluorogenic sensor that can reversibly bind to proteome amorphous aggregates and monitor their formation, transition, and clearance in live cells. This sensor was structurally optimized from previously reported fluorescent protein chromophores to enable noncovalent and reversible binding to aggregated proteins. Unlike all previous sensors, the noncovalent and reversible nature of this probe allows for dynamic detection of both the formation and clearance of aggregated proteome in one live-cell sample. Under different cellular stresses, this sensor reveals drastic differences in the morphology and location of aggregated proteome. Furthermore, we have shown that this sensor can detect the transition from proteome liquid-to-liquid phase separation to liquid-to-solid phase separation in a two-color imaging experiment. Overall, the sensor reported here can serve as a facile tool to screen therapeutic drugs and identify cellular pathways that ameliorate pathogenic proteome aggregation in live-cell models.

Short- and long-term outcomes of totally robotic versus robotic-assisted radical distal gastrectomy for advanced gastric cancer: a mono-institution retrospective study.

PURPOSE: By comparing short- and long-term outcomes following totally robotic radical distal gastrectomy (TRDG) and robotic-assisted radical distal gastrectomy (RADG), we aimed to assess in which modus operandi patients will benefit more. METHODS: From January 2015 to May 2019, we included 332 patients undergone RADG (237) and TRDG (95). Based on the propensity score matching (PSM), inclusion and exclusion criteria, 246 patients were finally included in the propensity score-matched cohort including RADG group (164) and TRDG group (82). We then compared the short- and long-term outcomes following both groups. RESULTS: Propensity score-matched cohort revealed no significant differences in both groups. Intra-abdominal bleeding, time to pass flatus, postoperative activity time, length of incision hospital stays, and stress response were significantly less in TRDG group than in RADG group. We observed 30 complications in RADG group while 13 complications in TRDG group. There were no significant differences in TRDG group and RADG group in terms of operation time, time for anastomosis, proximal resection, distal resection margin, number of lymph node resection, and total hospitalization cost. Both 3-year overall survival and 3-year disease-free survival were comparable in both groups. CONCLUSIONS: TRDG is a safe and feasible modus operandi profiting from short- and long-term outcomes compared with RADG. As surgeons improving their professional skills, TRDG could serve as the standard procedure for distal locally advanced gastric cancer with D2 lymphadenectomy.

Robotic-assisted versus conventional laparoscopic-assisted total gastrectomy with D2 lymphadenectomy for advanced gastric cancer: short-term outcomes at a mono-institution.

BACKGROUND: Robotic-assisted surgery, a developed technology, is becoming more and more accepted by surgeons. However, the comparison between robotic-assisted total gastrectomy (RATG) and conventional laparoscopy-assisted total gastrectomy (LATG) for advanced gastric cancer (AGC) is seldom reported, or usually the sample sizes reported are small. The current research was designed to compare the short-term outcomes of RATG and LATG with D2 lymphadenectomy for AGC in a mono-institution from China. METHODS: A total of 205 patients from June 2015 to October 2018 were included in this study. Among them, 106 patients underwent LATG, and 99 patients underwent RATG. The patients' clinicopathological characteristics, surgical performance and short-term outcomes were retrospectively analyzed. RESULTS: The clinicopathological characteristics showed no difference between the LATG group and the RATG group. However, compared with the LATG group, the operation time was longer (P = 0.000), and the operative blood loss (P = 0.000) and the volume of abdominal drainage was less (P = 0.000) in the RATG group. Moreover, the RATG took less time to remove abdominal drainage tube than LATG (P = 0.000). The plasma levels of CRP at 72 h post-operation was lower (P = 0.000), and the number of retrieved lymph nodes was more (P = 0.000) in the RATG group. Nevertheless, the postoperative length of stay (P = 0.890), the time to first flatus (P = 0.448), the postoperative complication (P = 0.915) and the visual analogue pain score at 24 h post-operation (P = 0.457) were comparable between the two groups. CONCLUSIONS: RATG with D2 lymphadenectomy shows safety and feasibility for AGC and could be served as an alternative treatment for AGC in the future.

Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway.

Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC.

High expression of partitioning defective 3-like protein is associated with malignancy in colorectal cancer.

Partitioning defective 3-like protein is a novel cell polarity protein. Recently, partitioning defective 3-like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3-like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3-like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues. We found that colorectal cancer tissues had much stronger partitioning defective 3-like protein immunoreactivity than normal tissues, and colorectal cancer patients with positive partitioning defective 3-like protein expression were characterized with higher cancer stages, metastasis, poor tumor differentiation, larger tumor size, as well as high levels of colorectal cancer markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning defective 3-like protein overexpression was independently predictive of lower survival rate in colorectal cancer patients, even after adjusting the influence of cofactors. Moreover, we also found that partitioning defective 3-like protein was associated with rapid growing colorectal cancer, while knockdown of partitioning defective 3-like protein expression largely inhibited cancer cell proliferation. Our study provided the first evidence that partitioning defective 3-like protein was overexpressed in colorectal cancer and associated with disease malignancy. Also, partitioning defective 3-like protein may serve as a promising prognostic marker and a potential therapeutic target for colorectal cancer treatment. Further study is necessary to understand the regulatory mechanism of partitioning defective 3-like protein in colorectal cancer and the feasibility of its application in clinic.

Unraveling the Interplay of Dopamine, Carbon Monoxide, and Heme Oxygenase in Neuromodulation and Cognition.

The dopaminergic system plays important roles in neuromodulation, including prominent roles in complex neurological functions such as cognition, reward, motivation, and memory. Understandably, the highly complex nature of such physiological functions means that their regulation is intertwined with other signaling pathways, as has been demonstrated by numerous studies. Contrary to its public perception of being poisonous at all concentrations, carbon monoxide (CO) is produced endogenously from heme degradation by heme oxygenase (HO) as part of the physiological process of red blood cell turnover. Physiological concentrations of CO can reach high micromolar ranges in the hemoglobin bound form. Low-dose CO has shown therapeutic effects in numerous animal models, including traumatic brain injury via engaging various hemoprotein targets. As such, the HO-CO axis has been shown to offer beneficial effects in organ protection, anti-inflammation, and neuroprotection, among many others. Further, a large number of publications have shown the interactions among CO, HO, and the dopaminergic system. In this review, we critically examine such experimental evidence in a holistic fashion and in the context of a possible dopamine-HO-CO signaling axis. We hope that this Perspective will stimulate additional investigations into the molecular connectivity related to this possible axis and open doors to the development of novel therapeutics that impact the dopaminergic system.

Carbon Monoxide as a Potential Therapeutic Agent: A Molecular Analysis of Its Safety Profiles.

Carbon monoxide (CO) is endogenously produced in mammals, with blood concentrations in the high micromolar range in the hemoglobin-bound form. Further, CO has shown therapeutic effects in various animal models. Despite its reputation as a poisonous gas at high concentrations, we show that CO should have a wide enough safety margin for therapeutic applications. The analysis considers a large number of factors including levels of endogenous CO, its safety margin in comparison to commonly encountered biomolecules or drugs, anticipated enhanced safety profiles when delivered via a noninhalation mode, and the large amount of safety data from human clinical trials. It should be emphasized that having a wide enough safety margin for therapeutic use does not mean that it is benign or safe to the general public, even at low doses. We defer the latter to public health experts. Importantly, this Perspective is written for drug discovery professionals and not the general public.

Identification method of thyroid nodule ultrasonography based on self-supervised learning dual-branch attention learning framework.

Thyroid ultrasound is a widely used diagnostic technique for thyroid nodules in clinical practice. However, due to the characteristics of ultrasonic imaging, such as low image contrast, high noise levels, and heterogeneous features, detecting and identifying nodules remains challenging. In addition, high-quality labeled medical imaging datasets are rare, and thyroid ultrasound images are no exception, posing a significant challenge for machine learning applications in medical image analysis. In this study, we propose a Dual-branch Attention Learning (DBAL) convolutional neural network framework to enhance thyroid nodule detection by capturing contextual information. Leveraging jigsaw puzzles as a pretext task during network training, we improve the network's generalization ability with limited data. Our framework effectively captures intrinsic features in a global-to-local manner. Experimental results involve self-supervised pre-training on unlabeled ultrasound images and fine-tuning using 1216 clinical ultrasound images from a collaborating hospital. DBAL achieves accurate discrimination of thyroid nodules, with a 88.5% correct diagnosis rate for malignant and benign nodules and a 93.7% area under the ROC curve. This novel approach demonstrates promising potential in clinical applications for its accuracy and efficiency.

Topologically Protected Quantum Logic Gates with Valley-Hall Photonic Crystals.

Topological photonics provide a promising way to realize more robust optical devices against some defects and environmental perturbations. Quantum logic gates are fundamental units of quantum computers, which are widely used in future quantum information processing. Thus, constructing robust universal quantum logic gates is an important way forward to practical quantum computing. However, the most important problem to be solved is how to construct the quantum-logic-gate-required 2 × 2 beam splitter with topological protection. Here, the experimental realization of the topologically protected contradirectional coupler is reported, which can be employed to realize the quantum logic gates, including control-NOT and Hadamard gates, on the silicon photonic platform. These quantum gates not only have high experimental fidelities but also exhibit a certain degree of tolerances against certain types of defects. This work paves the way for the development of practical optical quantum computations and signal processing.

Hyperbolic photonic topological insulators.

Topological photonics provides a new degree of freedom to robustly control electromagnetic fields. To date, most of established topological states in photonics have been employed in Euclidean space. Motivated by unique properties of hyperbolic lattices, which are regular tessellations in non-Euclidean space with a constant negative curvature, the boundary-dominated hyperbolic topological states have been proposed. However, limited by highly crowded boundary resonators and complicated site couplings, the hyperbolic topological insulator has only been experimentally constructed in electric circuits. How to achieve hyperbolic photonic topological insulators is still an open question. Here, we report the experimental realization of hyperbolic photonic topological insulators using coupled ring resonators on silicon chips. Boundary-dominated one-way edge states with pseudospin-dependent propagation directions have been observed. Furthermore, the robustness of edge states in hyperbolic photonic topological insulators is also verified. Our findings have potential applications in the field of designing high-efficient topological photonic devices with enhanced boundary responses.