Transition metal small clusters anchored on biphenylene for effective electrocatalytic nitrogen reduction.

The synthesis of ammonia via an electrochemical nitrogen reduction reaction (NRR, N2 + 6H+ + 6e- → 2NH3), which can weaken but not directly break an inert NN bond under mild conditions via multiple progressive protonation steps, has been proposed as one of the most attractive alternatives for the production of NH3. However, the development of appropriate catalyst materials is a major challenge in the application of NRRs. Recently, single- or multi-metal atoms anchored on two-dimensional (2D) substrates have been demonstrated as ideal candidates for facilitating NRRs. In this work, by applying spin-polarized density functional theory and ab initio molecular dynamic simulations, we systematically explored the performances of nine types of transition metal multi-atoms anchored on a recently developed 2D biphenylene (BPN) sheet in nitrogen reduction. Structural stability and NRR performance catalyzed by TMn (TM = V, Fe, Ni, Mo, Ru, Rh, W, Re, Ir; n = 1-4) clusters anchored on BPN sheets were systematically explored. After a strict six-step screening strategy, it was found that W2, Ru2 and Mo4 clusters loaded on BPN demonstrate superior potential for nitrogen reduction with extremely low onset potentials of -0.26, -0.36 and -0.17 V, respectively. Electronic structure analysis revealed that the enhanced ability of these multi-atom catalysts to effectively capture and reduce the N2 molecule can be attributed to bidirectional charge transfer between the d orbitals of transition metal atoms and molecular orbitals of the adsorbed N2 through a "donation-back donation" mechanism. Our findings highlight the value of BPN sheets as a substrate for designing multi-atom nitrogen reduction reaction catalysts.

Application of artificial intelligence-based dual-modality analysis combining fundus photography and optical coherence tomography in diabetic retinopathy screening in a community hospital.

BACKGROUND: To assess the feasibility and clinical utility of artificial intelligence (AI)-based screening for diabetic retinopathy (DR) and macular edema (ME) by combining fundus photos and optical coherence tomography (OCT) images in a community hospital. METHODS: Fundus photos and OCT images were taken for 600 diabetic patients in a community hospital. Ophthalmologists graded these fundus photos according to the International Clinical Diabetic Retinopathy (ICDR) Severity Scale as the ground truth. Two existing trained AI models were used to automatically classify the fundus images into DR grades according to ICDR, and to detect concomitant ME from OCT images, respectively. The criteria for referral were DR grades 2-4 and/or the presence of ME. The sensitivity and specificity of AI grading were evaluated. The number of referable DR cases confirmed by ophthalmologists and AI was calculated, respectively. RESULTS: DR was detected in 81 (13.5%) participants by ophthalmologists and in 94 (15.6%) by AI, and 45 (7.5%) and 53 (8.8%) participants were diagnosed with referable DR by ophthalmologists and by AI, respectively. The sensitivity, specificity and area under the curve (AUC) of AI for detecting DR were 91.67%, 96.92% and 0.944, respectively. For detecting referable DR, the sensitivity, specificity and AUC of AI were 97.78%, 98.38% and 0.981, respectively. ME was detected from OCT images in 49 (8.2%) participants by ophthalmologists and in 57 (9.5%) by AI, and the sensitivity, specificity and AUC of AI were 91.30%, 97.46% and 0.944, respectively. When combining fundus photos and OCT images, the number of referrals identified by ophthalmologists increased from 45 to 75 and from 53 to 85 by AI. CONCLUSION: AI-based DR screening has high sensitivity and specificity and may feasibly improve the referral rate of community DR.

Efficacy and Safety of Cetuximab Plus Cisplatin Alone or in Combination With Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma: A Randomized Trial.

OBJECTIVES: The aim of this study was to assess the clinical usefulness of cetuximab and cisplatin alone or in combination with paclitaxel as the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). METHODOLOGY: Three hundred patients with confirmed HNSCC from 20 different hospitals were included in this study. Patients in group I underwent a 2-hour infusion of 400 mg/m2 cetuximab (day 1), followed by a 1-hour infusion of 250 mg/m2 cetuximab weekly and 1-hour infusion of 100 mg/m2 cisplatin (days 1 and 21) per treatment cycle. Patients in group II were treated with a combination of cetuximab, cisplatin, and paclitaxel. Patients received 6 cycles of 175 mg/m2 paclitaxel given on days 1 and 21. The primary outcome of the study was progression-free survival (PFS); overall survival (OS) and objective response rate (ORR) were the secondary endpoints. RESULTS: The median PFS was 5 months and 8 months for patients in groups I and II, respectively (HR, 0.93; 95% CI, 0.85-1.78; P > 0.05). Similarly, we found no significant differences in OS between the 2 groups (median OS, 13 vs. 11 months, respectively; HR, 0.67; 95% CI, 0.42-1.43; P = 0.198). Moreover, we observed no significant difference in ORR between the 2 groups (ORR, 63.3% vs 69.9%, respectively; HR, 0.87; 95% CI, 0.36-1.67; P = 0.231). CONCLUSIONS: The combination of paclitaxel with cetuximab and cisplatin did not improve patient outcomes compared to cetuximab plus cisplatin alone. Therefore, the 2-drug regimen could be used as first-line treatment in patients with recurrent or metastatic HNSCC.

Changes in ocular biometric measurements after vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment repair.

BACKGROUND: To observe the changes in ocular biometric measurements after vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment (RRD) repair. METHODS: Sixty-three phakic, macula-off RRD eyes underwent vitrectomy with silicone oil tamponade but not lens extraction were included in this retrospective study. Measurements of axial length (AL), anterior chamber depth (ACD), lens thickness (LT) using the new Zeiss IOLMaster 700 and derivative lens position (LP), relative lens position (RLP) and lens-retina distance (LRD) were compared and analyzed between preoperative and postoperative in phakic, macula-off eyes with RRD. RESULTS: Preoperative AL, ACD, LT, LP, RLP and LRD were 24.94 ± 1.82 mm, 3.45 ± 0.42 mm, 4.34 ± 0.16 mm, 5.55 ± 0.41 mm, 0.22 ± 0.01 and 19.52 ± 1.82 mm. After a mean 4.85-month duration of silicone oil tamponade, postoperative AL, ACD, LT, LP, RLP and LRD were 25.42 ± 2.20 mm, 3.30 ± 0.41 mm, 4.43 ± 0.21 mm, 5.46 ± 0.40 mm, 0.22 ± 0.02 and 20.17 ± 2.36 mm, respectively. The differences in all measurements are significant (all P < 0.05). Preoperative AL and LRD are positively while RLP is negatively correlated with change in LRD. Change in AL but not in LT or LP is correlated with change in LRD. Biometric measurements except LT between preoperative and postoperative were in close agreement. CONCLUSION: The underestimation of AL and anterior shifting of lens in phakic, macula-off eyes with RRD after vitrectomy with silicone oil tamponade.

A high-salt diet aggravates retinal ischaemia/reperfusion injury.

Ischaemia/reperfusion contributes to the pathophysiological process of many retinal diseases. Previous studies have shown that retinal ischaemia/reperfusion mainly results in neuronal degeneration, including thinning of the retina, retinal ganglion cell death and reductions in electroretinography. A high-salt diet contributes to the inflammatory response and tissue hypoperfusion and may be associated with ischaemia/reperfusion injury. In the present study, we investigated the influence of a high-salt diet on retinal ischaemia/reperfusion injury and explored the potential mechanism in a rat model. The results revealed that the high-salt diet aggravated ischaemia/reperfusion-induced thinning of the retina. A TUNEL assay and Brn-3a staining revealed substantially more severe cell death and loss of retinal ganglion cells, and electroretinography confirmed worse retinal function in the ischaemia/reperfusion eyes of rats fed the high-salt diet. These effects may be associated with upregulation of Caspase-3, Bax, Interleukin-1ß and Interleukin-6 and decreased expression of nitric oxide. In summary, a high-salt diet aggravates ischaemia/reperfusion-induced retinal neuronal impairment by activating pro-apoptotic and pro-inflammatory signalling pathways and inhibiting vasodilation.

A rare variant between the left superior vena cava and the azygos vein.

During the educational dissection of a 68-year-old Chinese male cadaver, an azygos vein (AV) coursing on the left side with double superior vena cava was observed. The left superior vena cava (LSVC) began from the confluence of the left internal jugular and left subclavian veins, and extended downwards medially into the left edge of the dilated coronary sinus. The right superior vena cava was formed by the union of the right internal jugular and right subclavian veins, and drained into the right atrium from the above. The AV was formed by the union of the right and left ascending lumbar veins at the level of the tenth thoracic vertebra. It ascended along the left margin of the thoracic vertebra, receiving almost the bilateral posterior intercostal veins and then extended into the LSVC on the left wall via the azygos arch. Better understanding of these variations will reduce unnecessary and potential harmful testing, and unneeded patient anxiety.

VEGF Gene Polymorphisms are Associated with Risk of Tetralogy of Fallot.

BACKGROUND: The aim of this study was to investigate associations of 3 common polymorphisms in the VEGF gene, -2578C>A, -634C>G, and 936C>T, with risk of tetralogy of Fallot (TOF) in Chinese Han children. MATERIAL AND METHODS: From January 2010 to June 2013, a total of 400 pediatric subjects were recruited, including 160 cases with TOF (TOF group) and 240 healthy controls (control group). The genotypes of 3 common VEGF polymorphisms, -2578C>A, -634C>G, and 936C>T, were analyzed by polymerase chain reaction restriction fragment length polymorphism. All data were analyzed with SPSS 18.0 software. RESULTS: No significant differences were observed in body mass index or sex between TOF patients and controls (both P>0.05), but significant differences in age and family history of TOF were observed between the 2 groups (both P<0.05). The AA genotype in -2578C>A of VEGF was correlated with a significantly increased risk of TOF, and TOF risk in A allele carrier was 1.54-fold higher than that of C allele carrier (OR=1.54, 95%CI=1.14-2.09, P=0.005); the statistical significance was still present after Bonferroni correction (Pc=0.045). GG genotype in -634C>G of VEGF gene was also associated with an increased risk of TOF, and TOF risk in patients with G allele was 1.62-fold higher compared to patients with C allele (OR=1.62, 95%CI=1.19-2.21, P=0.002); the statistical significance was still present after Bonferroni correction (Pc=0.018). Interestingly, T allele in VEGF 936C>T polymorphism is associated with a decreased TOF risk (OR=0.65, 95%CI=0.49-0.87, P=0.003, the statistical significance was still present after Bonferroni correction (Pc=0.027). The result of logistic regression analysis revealed that -2578C>A, -634C>G, and 936C>T genotypes are independently related to the prevalence of TOF (all P<0.05). CONCLUSIONS: Our results confirmed that VEGF genetic polymorphisms, -2578C>A and -634C>G, may be associated with an increased TOF risk, while 936C>T polymorphism may be associated with decreased TOF risk.

[Ocular syndromes in patients with neurobrucellosis].

OBJECTIVE: To investigate the clinical features of ocular syndromes in patients with neurobrucellosis. METHOD: This is a retrospective series case study. The clinical data of 5 patients with neurobrucellosis, who were treated in Department of Neurology, Beijing Tongren Hospital, Captical Medical Uinversity, from May 2009 to January 2015, were collected. Their epidemiological information, clinical manifestation, laboratory and radiologic examination, therapy and prognosis were analyzed. RESULTS: Among the five patients, there were 3 males and 2 females, and their ages ranged from 20 to 67 years. The median age was 25 years. All patients had ever exposed to sheep. 1 patient lived close to a slaughterhouse and 2 patients lived in epidemic areas of brucellosis. 5 patients presented with binocular vision loss, 8 eyes with fundus edema, 3 patients with ophthalmoplegia;4 patients with fever,4 patients with headache,3 patients with neck stiffness,1 patient with movement and sensation disorders. Cerebrospinal fluid (CSF) pressure elevated, white cell number and protein increased with glucose reduction were detected respectively in 3 cases. While, CSF chloride decreased in 2 cases. Serum agglutination test for brucella was positive in 5 patients. Serum brucella culture was positive in 1 patient and CSF brucella culture was positive in 1 patient. Brain magnetic resonance imaging (MRI) showed that the optic nerve was involved in 3 patients,the meninges were involved in 1 patient and the brain white matter was involved in 1 patient. The combination of rifamycin, tetracycline, ceftriaxone sodium or quinolone were given to all patients and showed appreciated effects. CONCLUSIONS: The clinical features of ocular syndromes are atypical in patients with neurobrucellosis. Vision loss and ophthalmoplegia are more common to be seen. Neurobrucellosis should be considered when patients with ocular signs and other system symptoms without a definite diagnosis.

Intraocular lens tilt and decentration after primary and delayed implantation in phacovitrectomy for macula-off rhegmatogenous retinal detachment repair.

PURPOSE: To evaluate the tilt and decentration of intraocular lenses (IOLs) in eyes that underwent phacovitrectomy for macula-off rhegmatogenous retinal detachment (RRD) repair. METHODS: In this retrospective cohort study, 63 patients with macula-off RRD who underwent phacovitrectomy were enrolled and divided into a primary implantation group (group A) and a delayed implantation group (group B) according to the time of IOL implantation. Routine ocular examinations, including optometry, were performed, and the IOL tilt and decentration were measured. Postoperative refractive prediction error and IOL tilt and decentration were compared between the two groups, and the relevant factors of IOL positions were analyzed. RESULTS: The mean spherical refractive prediction error (MSE) was - 0.53 ± 0.39 D in group A and - 0.09 ± 0.55 in group B. The mean absolute spherical refractive prediction error (MASE) was 0.61 ± 0.23 D in group A and 0.50 ± 0.22 D in group B. The difference in MSE (t = -3.623, P < 0.05) but not in MASE (t = 1.866, P = 0.067) between the two groups was significant. The mean IOL tilt and mean decentration were 8.54° ±3.65° and 0.55 ± 0.18 mm in group A and 10.62° ±3.29° and 0.66 ± 0.14 mm, respectively, in Group B. Differences in tilt (t = -2.373, P < 0.05) and decentration (t = -2.698, P < 0.05) between the two groups were both significant. In group B, the mean time interval between phacovitrectomy and IOL implantation (TV-I) was 25.2 ± 6.9 weeks, and the absolute values of both IOL tilt and decentration were positively correlated with TV-I. CONCLUSION: In phacovitrectomy for macula-off RRD repair, primary IOL implantation leads to a postoperative myopic shift, while delayed IOL implantation may cause greater IOL tilt and decentration.

Natural products targeting autophagy and apoptosis in NSCLC: a novel therapeutic strategy.

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the predominant type. The roles of autophagy and apoptosis in NSCLC present a dual and intricate nature. Additionally, autophagy and apoptosis interconnect through diverse crosstalk molecules. Owing to their multitargeting nature, safety, and efficacy, natural products have emerged as principal sources for NSCLC therapeutic candidates. This review begins with an exploration of the mechanisms of autophagy and apoptosis, proceeds to examine the crosstalk molecules between these processes, and outlines their implications and interactions in NSCLC. Finally, the paper reviews natural products that have been intensively studied against NSCLC targeting autophagy and apoptosis, and summarizes in detail the four most retrieved representative drugs. This paper clarifies good therapeutic effects of natural products in NSCLC by targeting autophagy and apoptosis and aims to promote greater consideration by researchers of natural products as candidates for anti-NSCLC drug discovery.

Comparison of Barrett TK Universal II and Barrett Universal II TCRP Formulas in Power Calculations for 3 Presbyopia-Correcting Intraocular Lenses.

Purpose: To compare Barrett TK Universal II and Barrett Universal II TCRP calculations in the power calculations for 3 presbyopia-correcting intraocular lenses (PC-IOL). Methods: This observational study involved 64 eyes from 64 patients who prepared to undergo extraction of crystalline lenses combined with PC-IOL (Symfony ZXR00, PanOptix TFNT00, or AT LISA tri 839MP) implantation. All eyes underwent ocular biometric measurements with IOLMaster 700 and Pentacam HR, and the interdevice agreement of measurements including total keratometry (TK, IOLMaster 700) and total corneal refractive power (TCRP, Pentacam HR) was evaluated. IOL power calculations were performed using TK-based Barrett TK Universal II and TCRP-based Barrett Universal II calculations, respectively. Results: Paired t-tests showed that the differences in white-to-white diameter, central corneal thickness, anterior chamber depth, and mean TK between IOLMaster 700 and Pentacam HR were slight but significant (all P<0.05), and the differences in recommended IOL power for emmetropia between two Barrett calculations were also significant in 3 PC-IOLs (all P<0.05). The ROC curve showed that the AUC was 0.917 (95% CI, 0.820-0.971) for the absolute value of the difference between TK and TCRP in discriminating the difference of ≥ ±0.5 D in predicted IOL power with best cutoff values of 0.4 D. Conclusion: The novel Barrett TK Universal II formula built in IOLMaster 700 is comparable to TCRP-based Barrett Universal II calculation for IOL power calculation of PC-IOLs, and the convenience of using the Barrett TK Universal II formula should be founded on measurement consistency between devices.

Bilateral Femtosecond Laser-Assisted Clear Lens Extraction with Trifocal Intraocular Lens Implantation for Presbyopia Correction: A Short-Term Observational Study in Chinese Adults.

Purpose: To observe the outcome of bilateral femtosecond laser-assisted clear lens extraction with trifocal intraocular lens (IOL) implantation for presbyopia correction and evaluate its feasibility in early presbyopic adults. Methods: Prospective case series of eyes with clear crystalline lenses that underwent femtosecond laser-assisted lens extraction and trifocal IOL (Acrysof IQ PanOptix, Model TFNT00, Alcon) implantation between 2021 and 2023 were followed up for at least 3 months after surgery. Outcome measures included monocular uncorrected visual acuity at near (UNVA, 40 cm), intermediate (UIVA, 60 cm), and distance (UDVA, 5 m), monocular manifest refraction, corrected distance visual acuity (CDVA), defocus curve assessment, and spectacle independence at both near and distance. Results: A total of 60 eyes from 30 consecutive patients were included, and their mean age was 50.4±6.5 years. After surgery, the mean UNVA (LogMAR) increased from 0.28±0.16 to 0.08±0.07, UIVA increased from 0.25±0.12 to 0.09±0.06, and UDVA increased from 0.27±0.21 to 0.01±0.08. The enhancements of UNVA, UIVA and UDVA were all significant (P < 0.05). The optometric results showed that the mean postoperative spherical equivalent (SE) was -0.21±0.24 D, and the mean postoperative CDVA (LogMAR) was -0.00±0.06. The preoperative spectacle independences at near and distance were 46.7% (14/30) and 56.7% (17/30), respectively, and both increased to 100% at 3 months after surgery. Conclusion: Satisfactory visual outcomes and safe surgical procedures were observed in this study, which demonstrate that bilateral femtosecond laser-assisted clear lens extraction with PanOptix IOL implantation could be a feasible approach for presbyopia correction in working-age Chinese patients.

Thyroid dysfunction induced by anti-PD-1 therapy is associated with a better progression-free survival in patients with advanced carcinoma.

PURPOSE: Thyroid dysfunction is the most common immune-related adverse event during anti-programmed cell death 1 (anti-PD-1) therapy. In this study, we monitored patients with advanced malignant tumors who received anti-PD-1 therapy to observe the characteristic of anti-PD-1 therapy-induced thyroid dysfunction and its correlation with prognosis. METHODS: Patients with advanced carcinoma treated with anti-PD-1 therapy were evaluated for thyroid function at baseline and after treatment initiation from August 2020 to March 2022. Seventy-three patients were finally included in the study. RESULTS: Among these patients, 19 (26.03%) developed thyroid dysfunction after receiving anti-PD-1 therapy. Primary hypothyroidism and thyrotoxicosis were the most common clinical manifestation. Anti-PD-1-induced thyroid dysfunction occurred 63 (26-131) days after administration; thyrotoxicosis appeared earlier than primary hypothyroidism. In Kaplan-Meier survival analysis, the progression-free survival (PFS) of the thyroid dysfunction group was better than that of the no thyroid dysfunction group (227 (95% confidence interval (CI) 50.85-403.15) days vs 164 (95% CI 77.76-250.24) days, p = 0.026). Male patients had better PFS than female patients (213 (95% CI 157.74-268.26) days vs 74 (95% CI 41.23-106.77) days, p = 0.031). In cox proportional hazards regression model, anti-PD-1-induced thyroid dysfunction remained an independent predictor of better PFS (hazard ratio (HR) = 0.339(0.136-0.848), p = 0.021). CONCLUSION: Thyroid dysfunction is a common immune-related adverse events in advanced cancer patients treated with anti-PD-1 therapy and predicts a better prognosis. TRIAL REGISTRATION: This study was retrospectively registered with Trial ClinicalTrials.gov (NCT05593744) on October 25, 2022.

Microbiota-ear-brain interaction is associated with generalized anxiety disorder through activation of inflammatory cytokine responses.

Introduction: Generalized anxiety disorder (GAD) is one of the most enduring anxiety disorders, being associated with increased systemic inflammation. However, the trigger and mechanisms underlying the activation of inflammatory cytokine responses in GAD remain poorly understood. Materials and methods: We characterized the ear canal microbiome in GAD patients through 16S rRNA gene sequencing and metagenomic sequencing and identified the serum inflammatory markers in GAD patients. Spearman correlations were applied to test the relationship between the microbiota changes and systemic inflammation. Results: Our findings showed the higher microbial diversity, accompanied with the significantly increased abundance of Proteobacteria, and decreased abundance of Firmicutes in the ear canal of GAD participants compared to that of the age- and sex-matched healthy controls (HC). Metagenomic sequencing showed that Pseudomonas aeruginosa were significantly increased at species-level in GAD patients. Furthermore, we observed the relative abundance of Pseudomonas aeruginosa was positively associated with elevated systemic inflammatory markers and the severity of disease, suggesting that these ear canal microbiota alterations might be correlated with GAD by activating the inflammatory response. Conclusions: These findings indicate that microbiota-ear-brain interaction via upregulating inflammatory reaction involve in the development of GAD, as well as suggest that ear canal bacterial communities may be a target for therapeutic intervention.

Differences in Axial Length and IOL Power Based on Alternative A-Scan or Fellow-Eye Biometry in Macula-Off Rhegmatogenous Retinal Detachment Eyes.

INTRODUCTION: This study was performed to observe the potential refractive prediction error based on alternative A-scan ultrasound and fellow-eye biometry for phacovitrectomy in macula-off rhegmatogenous retinal detachment (RRD) eyes. METHODS: Phakic macula-off RRD eyes without axial length (AL) measurements obtained using IOLMaster were included. Vitrectomy without lens extraction was performed for RRD repair. Preoperative AL was measured using alternative A-scan ultrasound (AL-US). Postoperative AL was obtained in eyes with silicone oil tamponade (AL-SO) and preoperative fellow-eye biometry (AL-FE) using IOLMaster. Other eyes that faced the same preoperative situation but underwent phacovitrectomy based on fellow-eye biometry were recruited as controls. RESULTS: AL-US, AL-FE, and AL-SO were 25.39 ± 2.14 mm, 25.85 ± 2.16 mm and 26.08 ± 2.53 mm, respectively. The Bland-Altman agreement among AL-US, AL-FE and AL-SO was good (95.5%, 21/22 of cases were in the LoA). The mean IOL power calculated using AL-US (Power-US), AL-FE (Power-FE) and AL-SO (Power-SO) was 16.81 ± 7.19 D, 14.74 ± 6.95 D and 13.54 ± 8.32 D, respectively. The difference between AL-US and AL-SO was significant (P < 0.05), while that between AL-FE and AL-SO was not (P > 0.05). The difference between Power-US and Power-SO was significant (P < 0.05), while that between Power-FE and Power-SO was not (P > 0.05). Nine eyes underwent phacovitrectomy based on fellow-eye biometry and had a final postoperative myopic shift of 0.64 ± 0.78 D. CONCLUSIONS: Alternative A-scan ultrasound led to a significant difference in AL and a prediction error in IOL power, while fellow-eye biometry provided similar results to silicone oil-filled eyes after RRD repair.

COVID-19 vaccine hesitancy cannot fully explain disparities in vaccination coverage across the contiguous United States.

Vaccine hesitancy has been identified as a major obstacle preventing comprehensive coverage against the COVID-19 pandemic. However, few studies have analyzed the association between ex-ante vaccine hesitancy and ex-post vaccination coverage. This study leveraged one-year county-level data across the contiguous United States to examine whether the prospective vaccine hesitancy eventually translates into differential vaccination rates, and whether vaccine hesitancy can explain socioeconomic, racial, and partisan disparities in vaccine uptake. A set of structural equation modeling was fitted with vaccine hesitancy and vaccination rate as endogenous variables, controlling for various potential confounders. The results demonstrated a significant negative link between vaccine hesitancy and vaccination rate, with the difference between the two continuously widening over time. Counties with higher socioeconomic statuses, more Asian and Hispanic populations, more elderly residents, greater health insurance coverage, and more Democrats presented lower vaccine hesitancy and higher vaccination rates. However, underlying determinants of vaccination coverage and vaccine hesitancy were divergent regarding their different associations with exogenous variables. Mediation analysis further demonstrated that indirect effects from exogenous variables to vaccination coverage via vaccine hesitancy only partially explained corresponding total effects, challenging the popular narrative that portrays vaccine hesitancy as a root cause of disparities in vaccination. Our study highlights the need of well-funded, targeted, and ongoing initiatives to reduce persisting vaccination inequities.

Engineering Metabolic Pathways for Cofactor Self-Sufficiency and Serotonin Production in Escherichia coli.

Serotonin is a neurotransmitter that plays an essential regulatory role in numerous cognitive and behavioral functions. Recent advances in synthetic biology have enabled engineering of non-natural biosynthetic pathways for serotonin production in E. coli. Here, an optimized heterologous serotonin biosynthetic pathway was engineered in E. coli and coupled with the biosynthetic and regeneration modules of the endogenous vital cofactor tetrahydrobiopterin (BH4) for efficient serotonin production using whole-cell catalysis. Further metabolic engineering efforts were performed to ensure an adequate endogenous BH4 supply, including enhancements of GTP biosynthesis and intracellular reducing power availability. Using the optimized fed-batch fermentation, an overall maximum serotonin yield of 40.3% (mol/mol) and a peak titer of 1.68 g/L (production rate of 0.016 g/L/h) were achieved. The strategies employed in this study show the promise of using E. coli for pterin self-sufficiency and high-level serotonin production, and the engineered strains hold the potential for use in industrial applications.

Measurement of Iris Thickness at Different Regions in Healthy Chinese Adults.

PURPOSE: To study the variation of iris thicknesses in different regions and explore the possible correlations with age and gender. METHODS: Healthy Chinese adults were recruited; the anterior segment of their eyes was imaged by swept-source optical coherence tomography (SS-OCT). The horizontal scan of the right eye was selected, and the thicknesses of both the nasal and temporal irises were measured at 199 evenly spaced points. RESULTS: A total of 233 subjects with an average age of 36.79 ± 10.04 years (range 19 to 62) were included in the final analysis. The mean iris thicknesses of the temporal and nasal sides were 364.79 ± 47.58 µm and 372.44 ± 43.75 µm, respectively. The mean nasal iris thickness was positively correlated with age (ß = 0.9 µm/year; P = 0.002), but the temporal one was not (ß = 0.077 µm/year; P = 0.806). At 139 points of the nasal iris and 146 points of the temporal iris, the iris thickness was significantly correlated with age (P < 0.05). The thicknesses of the peripheral and pupillary parts were positively correlated with age, while the middle part was negatively correlated with age. No significant difference was observed in the mean iris thickness between genders (temporal: t = 1.597, P = 0.112; nasal: t = 1.870, P = 0.063), but females had a thicker iris than males at 50 points in the temporal side and 49 points in the nasal side (P < 0.05); no point in males was observed to have thicker iris compared to females. CONCLUSION: Using SS-OCT and the novel method, thicknesses of the iris at different regions were measured. The thicknesses of the peripheral and pupillary irises increase with age, while the thicknesses of the middle part decrease.

High-Level Production of Indole-3-acetic Acid in the Metabolically Engineered Escherichia coli.

Indole-3-acetic acid (IAA) is a critical plant hormone that regulates cell division, development, and metabolism. IAA synthesis in plants and plant-associated microorganisms cannot fulfill the requirement for large-scale agricultural production. Here, two novel IAA biosynthesis pathways, tryptamine (TAM) and indole-3-acetamide (IAM), were developed for IAA production by whole-cell catalysis and de novo biosynthesis in an engineered Escherichia coli MG1655. When 10 g/L l-tryptophan was used as a substrate, an MIA-6 strain containing a heterologous IAM pathway had the highest IAA titer of 7.10 g/L (1.34 × 103 mg/g DCW), which was 98.4 times more than MTAI-5 containing the TAM pathway by whole-cell catalysis. De novo IAA biosynthesis was optimized by improving NAD(P)H availability, resulting in an increased IAA titer of 906 mg/L obtained by the MGΔadhE::icd strain, which is 29.7% higher than the control. These strategies exhibit the potential for IAA production in engineered E. coli and possible industrial applications.

Microscope-integrated Intraoperative Optical Coherence Tomography for Anterior Segment Surgical Maneuvers.

Purpose: To evaluate the potential value of microscope-integrated optical coherence tomography (MI-OCT) in anterior segment surgical maneuvers. Methods: Twenty-four ophthalmology residents, who were randomly and evenly divided into two groups, performed four anterior segment surgical maneuvers (corneal tunnel, scleral tunnel, simple corneal suture, and corneal laceration repair) on porcine eyes with (group B) or without (group A) real-time MI-OCT feedback. All residents performed the maneuvers again without MI-OCT. Results: Compared with group A, group B (with MI-OCT) showed better accuracy in the length/depth of the corneal tunnel and the length of the scleral tunnel. However, both groups showed similar performances in the depth of both the simple corneal suture and the corneal laceration suture. When both groups performed the maneuvers again without MI-OCT, group B still showed better results than group A for the length of both the corneal and scleral tunnels. Conclusions: Primary results suggest that real-time MI-OCT images are valuable for some anterior segment surgical maneuvers and could be helpful in surgical training. Translational Relevance: MI-OCT systems can be valuable in improving accuracy and decision making during anterior segment surgery and will be useful in surgical training.