A Food Odorant, α-Ionone, Inhibits Skin Cancer Tumorigenesis by Activation of OR10A6.

SCOPE: This study aims to investigate the anticancer properties of α-ionone in squamous cell carcinoma (SCC). METHODS AND RESULTS: The expression of OR10A6 together with olfactory receptor signaling components is demonstrated in A431 human SCC cells via RT-PCR and qRT-PCR analysis. OR10A6 activation in A431 cells using the ligand α-ionone inhibits proliferation and migration but induces apoptosis which is confirmed by proliferation assay, colony formation, and western blotting. The mechanism involves the core proteins of the Hippo pathway, where the phosphorylation of large tumor suppressor kinase (LATS), yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) is confirmed by western blotting. However, the anticancer effects of α-ionone are abrogated in A431 cells with OR10A6 gene knockdown. In A431 xenograft mouse model, the injection of α-ionone suppresses tumor growth, induces apoptosis, and increases phosphorylation of the LATS-YAP-TAZ signaling axis in the Hippo pathway. None of these effects are observed in xenografted tumors with OR10A6 gene knockdown. CONCLUSION: These findings collectively demonstrate that activation of ectopic OR OR10A6 by α-ionone in SCC cells stimulates the Hippo pathway and suppresses tumorigenesis both in vitro and in vivo, suggesting a novel therapeutic candidate for the treatment of SCC.

Unveiling the Potential of Natural Compounds: A Comprehensive Review on Adipose Thermogenesis Modulation.

The process of adipocyte browning has recently emerged as a novel therapeutic target for combating obesity and obesity-related diseases. Non-shivering thermogenesis is the process of biological heat production in mammals and is primarily mediated via brown adipose tissue (BAT). The recruitment and activation of BAT can be induced through chemical drugs and nutrients, with subsequent beneficial health effects through the utilization of carbohydrates and fats to generate heat to maintain body temperature. However, since potent drugs may show adverse side effects, nutritional or natural substances could be safe and effective as potential adipocyte browning agents. This review aims to provide an extensive overview of the natural food compounds that have been shown to activate brown adipocytes in humans, animals, and in cultured cells. In addition, some key genetic and molecular targets and the mechanisms of action of these natural compounds reported to have therapeutic potential to combat obesity are discussed.

The Anticancer Activities of Natural Terpenoids That Inhibit Both Melanoma and Non-Melanoma Skin Cancers.

The prevalence of two major types of skin cancer, melanoma and non-melanoma skin cancer, has been increasing worldwide. Skin cancer incidence is estimated to rise continuously over the next 20 years due to ozone depletion and an increased life expectancy. Chemotherapeutic agents could affect healthy cells, and thus may be toxic to them and cause numerous side effects or drug resistance. Phytochemicals that are naturally occurring in fruits, plants, and herbs are known to possess various bioactive properties, including anticancer properties. Although the effects of phytochemicals are relatively milder than chemotherapeutic agents, the long-term intake of phytochemicals may be effective and safe in preventing tumor development in humans. Diverse phytochemicals have shown anti-tumorigenic activities for either melanoma or non-melanoma skin cancer. In this review, we focused on summarizing recent research findings of the natural and dietary terpenoids (eucalyptol, eugenol, geraniol, linalool, and ursolic acid) that have anticancer activities for both melanoma and non-melanoma skin cancers. These terpenoids may be helpful to protect skin collectively to prevent tumorigenesis of both melanoma and nonmelanoma skin cancers.

Enhancing Single Photon Emission Purity via Design of van der Waals Heterostructures.

Quantum emitters are essential components of quantum photonic circuitry envisioned beyond the current optoelectronic state-of-the-art. Two dimensional materials are attractive hosts for such emitters. However, the high single photon purity required is rarely realized due to the presence of spectrally degenerate classical light originating from defects. Here, we show that design of a van der Waals heterostructure effectively eliminates this spurious light, resulting in purities suitable for a variety of quantum technological applications. Single photon purity from emitters in monolayer WSe2 increases from 60% to 92% by incorporating this monolayer in a simple graphite/WSe2 heterostructure. Fast interlayer charge transfer quenches a broad photoluminescence background by preventing radiative recombination through long-lived defect bound exciton states. This approach is generally applicable to other 2D emitter materials, circumvents issues of material quality, and offers a path forward to achieve the ultrahigh single photon purities ultimately required for photon-based quantum technologies.

Development of a novel prediction model for differential diagnosis between spinal myxopapillary ependymoma and schwannoma.

Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic resonance imaging (MRI) characteristics. We aimed to identify significant MRI features that can differentiate between MPE and schwannoma and develop a novel prediction model using these features. In this study, 77 patients with MPE (n = 24) or schwannoma (n = 53) who underwent preoperative MRI and surgical removal between January 2012 and December 2022 were included. MRI features, including intratumoral T2 dark signals, subarachnoid hemorrhage (SAH), leptomeningeal seeding, and enhancement patterns, were analyzed. Logistic regression analysis was conducted to distinguish between MPE and schwannomas based on MRI parameters, and a prediction model was developed using significant MRI parameters. The model was validated internally using a stratified tenfold cross-validation. The area under the curve (AUC) was calculated based on the receiver operating characteristic curve analysis. MPEs had a significantly larger mean size (p = 0.0035), higher frequency of intratumoral T2 dark signals (p = 0.0021), associated SAH (p = 0.0377), and leptomeningeal seeding (p = 0.0377). Focal and diffuse heterogeneous enhancement patterns were significantly more common in MPEs (p = 0.0049 and 0.0038, respectively). Multivariable analyses showed that intratumoral T2 dark signal (p = 0.0439) and focal (p = 0.0029) and diffuse enhancement patterns (p = 0.0398) were independent factors. The prediction model showed an AUC of 0.9204 (95% CI 0.8532-0.9876) and the average AUC for internal validation was 0.9210 (95% CI 0.9160-0.9270). MRI provides useful data for differentiating spinal MPEs from schwannomas. The prediction model developed based on the MRI features demonstrated excellent discriminatory performance.

Surgical treatment of spondylolisthesis by oblique lumbar interbody fusion and transpedicular screw fixation: Comparison between conventional double position versus navigation-assisted single lateral position.

BACKGROUND AND OBJECTIVES: Oblique lumbar interbody fusion (OLIF) procedures involve anterior insertion of interbody cage in lateral position. Following OLIF, insertion of pedicle screws and rod system is performed in a prone position (OLIF-con). The location of the cage is important for restoration of lumbar lordosis and indirect decompression. However, inserting the cage at the desired location is difficult without reduction of spondylolisthesis, and reduction after insertion of interbody cage may limit the amount of reduction. Recent introduction of spinal navigation enabled both surgical procedures in one lateral position (OLIF-one). Therefore, reduction of spondylolisthesis can be performed prior to insertion of interbody cage. The objective of this study was to compare the reduction of spondylolisthesis and the placement of cage between OLIF-one and OLIF-con. METHODS: We retrospectively reviewed 72 consecutive patients with spondylolisthesis for this study; 30 patients underwent OLIF-one and 42 underwent OLIF-con. Spinal navigation system was used for OLIF-one. In OLIF-one, the interbody cage was inserted after reducing spondylolisthesis, whereas in OLIF-con, the cage was inserted before reduction. The following parameters were measured on X-rays: pre- and postoperative spondylolisthesis slippage, reduction degree, and the location of the cage in the disc space. RESULTS: Both groups showed significant improvement in back and leg pains (p < .05). Transient motor or sensory changes occurred in three patients after OLIF-con and in two patients after OLIF-one. Pre- and postoperative slips were 26.3±7.7% and 6.6±6.2% in OLIF-one, and 23.1±7.0% and 7.4±5.8% in OLIF-con. The reduction of slippage was 74.4±6.3% after OLIF-one and 65.4±5.7% after OLIF-con, with a significant difference between the two groups (p = .04). The cage was located at 34.2±8.9% after OLIF-one and at 42.8±10.3% after OLIF-con, with a significant difference between the two groups (p = .004). CONCLUSION: Switching the sequence of surgical procedures with OLIF-one facilitated both the reduction of spondylolisthesis and the placement of the cage at the desired location.

Role of Stem Cell-Derived Exosomes and microRNAs in Spinal Cord Injury.

Neurological disorders represent a global health problem. Current pharmacological treatments often lead to short-term symptomatic relief but have dose-dependent side effects, such as inducing orthostatic arterial hypotension due to the blockade of alpha receptors, cardiotoxic effects due to impaired repolarization, and atrioventricular block and tachycardia, including ventricular fibrillation. These challenges have driven the medical community to seek effective treatments for this serious global health threat. Mesenchymal stem cells (MSCs) are pluripotent cells with anti-inflammatory, anti-apoptotic, and immunomodulatory properties, providing a promising alternative due to their ability to differentiate, favorable culture conditions, in vitro manipulation ability, and robust properties. Although MSCs themselves rarely differentiate into neurons at the site of injury after transplantation in vivo, paracrine factors secreted by MSCs can create environmental conditions for cell-to-cell communication and have shown therapeutic effects. Recent studies have shown that the pleiotropic effects of MSCs, particularly their immunomodulatory potential, can be attributed primarily to these paracrine factors. Exosomes derived from MSCs are known to play an important role in these effects. Many studies have evaluated the potential of exosome-based therapies for the treatment of various neurological diseases. In addition to exosomes, various miRNAs derived from MSCs have been identified to regulate genes and alleviate neuropathological changes in neurodegenerative diseases. This review explores the burgeoning field of exosome-based therapies, focusing on the effects of MSC-derived exosomes and exosomal miRNAs, and summarizes recent findings that shed light on the potential of exosomes in the treatment of neurological disorders. The insights gained from this review may pave the way for innovative and effective treatments for these complex conditions. Furthermore, we suggest the therapeutic effects of exosomes and exosomal miRNAs from MSCs, which have a rescue potential in spinal cord injury via diverse signaling pathways.

OR2H2 Activates CAMKKß-AMPK-Autophagy Signaling Axis and Suppresses Senescence in VK2/E6E7 Cells.

Olfactory receptors are expressed in multiple extra-nasal tissues and these ectopic olfactory receptors mediate tissue-specific functions and regulate cellular physiology. Ectopic olfactory receptors may play key roles in tissues constantly exposed to odorants, thus the functionality of these receptors in genital tissues is of particular interest. The functionality of ectopic olfactory receptors expressed in VK2/E6E7 human vaginal epithelial cells was investigated. OR2H2 was the most highly expressed olfactory receptor expressed in VK2/E6E7 cells, and activation of OR2H2 by aldehyde 13-13, a ligand of OR2H2, increased the intracellular calcium and cAMP concentrations. Immunoblotting demonstrated that activation of OR2H2 by aldehyde 13-13 stimulated the CAMKKß-AMPK-mTORC1-autophagy signaling axis, and that these effects were negated by OR2H2 knockdown. AMPK is known to regulate senescence; consequently, we investigated further the effect of aldehyde 13-13 on senescence. In H2O2-induced senescent cells, activation of OR2H2 by aldehyde 13-13 restored proliferation, and reduced the expression of senescence markers, P16 and P19. Additionally, aldehyde 13-13 induced apoptosis of H2O2-induced senescent cells, compared with non-senescent normal cells. In vivo, aldehyde 13-13 increased the lifespan of Caenorhabditis elegans and budding yeast. These findings demonstrate that OR2H2 is a functional receptor in VK2/E6E7 cells, and that activation of OR2H2 activates the AMPK-autophagy axis, and suppresses cellular aging and senescence, which may increase cellular health.

Revisiting En Bloc Resection Versus Piecemeal Resection for the Treatment of Giant Cell Tumor of the Spine.

OBJECTIVE: Surgery for spinal giant cell tumors (GCTs) is challenging because these tumors often exhibit a poor clinical course owing to their locally aggressive features. This study aimed to investigate the prognostic factors of GCT recurrence in the spine by focusing on surgical factors. METHODS: We retrospectively reviewed patients who underwent surgery for spinal GCTs between January 2005 and December 2016. Using the Kaplan-Meier method, surgical variables were evaluated for disease-free survival (DFS). Since tumor violation may occur at the pedicle during en bloc resection of the spine, it was further analyzed as a separate variable. Multivariate Cox proportional hazard regression analysis was performed for other clinical and radiographic variables. A total of 28 patients (male:female = 8:20) were included. The mean follow-up period was 90.5 months (range, 15-184 months). RESULTS: Among the 28 patients, gross total resection (GTR) was the most important factor for DFS (P = 0.001). Any form of tumor violation was also correlated with DFS (P = 0.049); however, use of en bloc resection technique did not show a significant DFS gain compared to piecemeal resection (P = 0.218). In the patient group that achieved GTR, the mode of resection was not a significant factor for DFS (P = 0.959). In the multivariate analysis, the extent of resection was the only significant variable that affected DFS (P = 0.016). CONCLUSIONS: Conflicting results on tumor violation from univariate and multivariate analyses suggest that GTR without tumor violation should be the treatment goal for spinal GCTs. However, when tumor violation is unavoidable, it would be important to prioritize GTR over adhering to en bloc resection.

Impact on Spine Surgery during the First Two Years of COVID-19 Pandemic: A Nationwide Study in South Korea.

Since December 2019, the novel coronavirus (COVID-19) has infected people worldwide. Owing to its rapid spread, elective surgeries, including spine surgery, have been re-scheduled. We analyzed nationwide data to investigate changes in the volume of spine surgery during the first two years of the pandemic. Nationwide data from January 2016 to December 2021 were obtained. We compared the total number of patients who underwent spine surgery and related medical expenses before and during the COVID-19 pandemic. In February and September, the number of patients was significantly smaller compared to January and August, respectively. Despite the pandemic, the proportion of patients undergoing spine surgery for degenerative diseases in 2021 was the highest. In contrast, the proportions of patients undergoing spine surgery for tumors showed a continuous decrease from 2019 to 2021. Although the number of spine surgeries performed at tertiary hospitals was lowest in 2020, it was not significantly smaller than that in 2019.The number of patients who underwent spine surgery in March 2020, during the first outbreak, decreased compared to the previous month, which differed from the trend observed in the pre-COVID-19 period. However, as the pandemic continues, the impact of COVID-19 on spine surgery has become less evident.

Effects of tomato ketchup and tomato paste extract on hepatic lipid accumulation and adipogenesis.

Tomatoes include high levels of lycopene, which is a potent antioxidative, hypolipidemic, and antidiabetic phytochemical. The intake of lycopene is associated with a reduced risk of insulin resistance and metabolic syndrome. The aim of this study was to investigate whether tomato ketchup and tomato paste, major dietary sources for tomato and lycopene, could regulate hepatic lipid metabolism and adipogenesis. To investigate the regulatory effects of tomato ketchup and tomato paste, we prepared a tomato ketchup extract (TKE) and a tomato paste extract (TPE) in 80% (v/v) ethyl acetate for the experiment. TKE and TPE reduced lipid accumulation and key markers for gluconeogenesis and induced a higher rate of fatty acid oxidation in HepG2 hepatocytes. In 3T3-L1 adipocytes, TKE and TPE increased adipogenesis and intracellular triglyceride accumulation, and stimulated glucose uptake. Peroxisome proliferator-activated receptor alpha and gamma expression levels were increased by TKE and TPE treatment. A single oral dose of tomato ketchup and tomato paste (9.28 g/kg) significantly improved glucose and insulin tolerance in mice. These findings suggest that lycopene-containing tomato ketchup and tomato paste may have beneficial regulatory effects in terms of energy metabolism in hepatocytes and adipocytes, and thus may improve blood glucose metabolism.

Dural rupture and subsequent spinal cord herniation due to closed wound suction drainage after spinal surgery.

Closed wound suction drains are commonly used in spinal surgery. Severe neurological complications related to their use are rare. Here, we report a case of a dural rupture and subsequent spinal cord herniation related to the use of closed suction drains after posterior decompression and fixation surgery for spinal metastasis.

Long-term Follow-up Results of Reconstructive Laminoplasty With L-shaped Leibinger Mini-plate for Posterior Approach in the Treatment of Intraspinal Tumor Surgery.

OBJECTIVE: Laminoplasty using mini-plates is one of the most common surgical techniques in surgery for intraspinal pathologies. However, limited are present in the literature. The aim of this study was to determine its long-term clinical and radiologic outcome, specifically using an L-shaped mini-plate. METHODS: Patients who underwent surgery for spinal intradural pathology from January 2008 to December 2019 were retrospectively reviewed. Those who received laminoplasty using the Leibinger mini-plate and were followed for more than 2 years were included. Patient demographics and clinical and radiographic data were reviewed and analyzed. A total of 117 patients (male:female = 47:70; mean age 50.9 years, range 16-92 years) were included, and mean follow-up period was 50.3 months (range 24-151 months). RESULTS: The most common pathology was schwannoma (n = 66, 56.4%) followed by meningioma (n = 30, 25.6%). Gross total resection was achieved in 82.9% (n = 97). Clinical outcomes at last follow-up were mostly good and excellent (n = 95, 81.2%). Computed tomography at the postoperative 1-year follow-up were available in 32 patients (27.4%) and the overall fusion rate was 89.3% (50 of 56 laminae). The fusion rate was significantly lower in the cervical spine compared to other locations (50% vs. thoracic [100%], lumbar [85.7%], P < 0.002). No displacement of laminae or postoperative spinal deformity were observed throughout the follow-up. CONCLUSIONS: Laminoplasty using L-shape Leibinger mini-plates had an 89.3% fusion rate, and no displacement of the re-attached laminae was observed. We think it is a safe and feasible option in surgeries for intraspinal pathologies.

Advances in Neural Stem Cell Therapy for Spinal Cord Injury: Safety, Efficacy, and Future Perspectives.

Spinal cord injury (SCI) is a devastating central nervous system injury that leads to severe disabilities in motor and sensory functions, causing significant deterioration in patients' quality of life. Owing to the complexity of SCI pathophysiology, there has been no effective treatment for reversing neural tissue damage and recovering neurological functions. Several novel therapies targeting different stages of pathophysiological mechanisms of SCI have been developed. Among these, treatments using stem cells have great potential for the regeneration of damaged neural tissues. In this review, we have summarized recent preclinical and clinical studies focusing on neural stem cells (NSCs). NSCs are multipotent cells with specific differentiation capabilities for neural lineage. Several preclinical studies have demonstrated the regenerative effects of transplanted NSCs in SCI animal models through both paracrine effects and direct neuronal differentiation, restoring synaptic connectivity and neural networks. Based on the positive results of several preclinical studies, phase I and II clinical trials using NSCs have been performed. Despite several hurdles and issues that need to be addressed in the clinical use of NSCs in patients with SCI, gradual progress in the technical development and therapeutic efficacy of NSCs treatments has enhanced the prospects for cell-based treatments in SCI.

Suppressing ion migration in metal halide perovskite via interstitial doping with a trace amount of multivalent cations.

Cations with suitable sizes to occupy an interstitial site of perovskite crystals have been widely used to inhibit ion migration and promote the performance and stability of perovskite optoelectronics. However, such interstitial doping inevitably leads to lattice microstrain that impairs the long-range ordering and stability of the crystals, causing a sacrificial trade-off. Here, we unravel the evident influence of the valence states of the interstitial cations on their efficacy to suppress the ion migration. Incorporation of a trivalent neodymium cation (Nd3+) effectively mitigates the ion migration in the perovskite lattice with a reduced dosage (0.08%) compared to a widely used monovalent cation dopant (Na+, 0.45%). The photovoltaic performances and operational stability of the prototypical perovskite solar cells are enhanced with a trace amount of Nd3+ doping while minimizing the sacrificial trade-off.

OR2AT4, an Ectopic Olfactory Receptor, Suppresses Oxidative Stress-Induced Senescence in Human Keratinocytes.

Olfactory receptors (ORs) are the largest protein superfamily in mammals. Certain ORs are ectopically expressed in extranasal tissues and regulate cell type-specific signal transduction pathways. OR2AT4 is ectopically expressed in skin cells and promotes wound healing and hair growth. As the capacities of wound healing and hair growth decline with aging, we investigated the role of OR2AT4 in the aging and senescence of human keratinocytes. OR2AT4 was functionally expressed in human keratinocytes (HaCaT) and exhibited co-expression with G-protein-coupled receptor signaling components, Golfα and adenylate cyclase 3. The OR2AT4 ligand sandalore modulates the intracellular calcium, inositol phosphate, and cyclic adenosine monophosphate (cAMP) levels. The increased calcium level induced by sandalore was attenuated in cells with OR2AT4 knockdown. OR2AT4 activation by sandalore inhibited the senescent cell phenotypes and restored cell proliferation and Ki-67 expression. Sandalore also inhibited the expression of senescence-associated ß-galactosidase and increased p21 expression in senescent HaCaT cells in response to hydrogen peroxide. Additionally, sandalore activated the CaMKKß/AMPK/mTORC1/autophagy signaling axis and promoted autophagy. OR2AT4 knockdown attenuated the increased in the intracellular calcium level, cell proliferation, and AMPK phosphorylation induced by sandalore. These findings demonstrate that the effects of sandalore are mediated by OR2AT4 activation. Our findings suggest that OR2AT4 may be a novel therapeutic target for anti-aging and anti-senescence in human keratinocytes.

Mechanism of Action of Cyanidin 3-O-Glucoside in Gluconeogenesis and Oxidative Stress-Induced Cancer Cell Senescence.

Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin abundant in fruits and vegetables that interacts and possibly modulates energy metabolism and oxidative stress. This study investigated the effect of C3G on gluconeogenesis and cancer cell senescence. C3G activates adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor involved in metabolism and the aging process. C3G suppressed hepatic gluconeogenesis by reducing the expression of gluconeogenic genes through the phosphorylation inactivation of CRTC2 and HDAC5 coactivators via AMPK. C3G did not directly interact with AMPK but, instead, activated AMPK through the adiponectin receptor signaling pathway, as demonstrated through adiponectin receptor gene knockdown experiments. In addition, C3G increased cellular AMP levels in cultured hepatocytes, and the oral administration of C3G in mice elevated their plasma adiponectin concentrations. These effects collectively contribute to the activation of AMPK. In addition, C3G showed potent antioxidant activity and induced cellular senescence, and apoptosis in oxidative-stress induced senescence in hepatocarcinoma cells. C3G increased senescence-associated ß-galactosidase expression, while increasing the expression levels of P16, P21 and P53, key markers of cellular senescence. These findings demonstrate that anthocyanin C3G achieves hypoglycemic effects via AMPK activation and the subsequent suppression of gluconeogenesis and exhibits anti-cancer activity through the induction of apoptosis and cellular senescence.

Evaluating medical students' ability to identify and report errors: finding gaps in patient safety education.

BACKGROUND: Although there are frequent complaints of medical students' incompetence in reporting errors, few studies have examined their error-reporting abilities in the real world. OBJECTIVES: Three sub-functions of self-regulation theory were used to evaluate medical students' ability to identify errors (self-monitoring), analyse root causes (self-judgment), and devise improvement plans (self-reactions). In addition, whether students reacted differently to their errors and those of others (three sub-functions) was also examined. METHODS: A total of 952 patient safety reports were reviewed retrospectively, submitted by third-year medical students between 2016 and 2018. Data were quantitatively and qualitatively analysed to investigate who committed the error, to identify the type of error and its root causes, and to find suggested improvement plans. Chi-square and Fisher's exact tests were used to compare students' responses to error origins. RESULTS: Students reported other errors more frequently than their own (67.6% vs. 32.4%). They reported common critical medical errors, including errors related to engaging with patients (34.5%), invasive procedures (20.2%), and infection (18.5%). The root causes identified were more precise than the improvement plans by the students (75.5% vs. 18.4%, respectively). The students' improvement plans were not practical, especially at the patient level (25.8%). When students committed errors, they considered human factors such as fatigue, scheduling, and training as the most common root cause, focussing on improvement plans at the individual level. CONCLUSIONS: The results suggest that students were good at self-judgment, but not at self-monitoring and self-reactions. They reacted differently, based on who committed the error. To enhance self-regulated learning, Educators should encourage students to confront their errors, reflect on their self-reactions towards errors, develop well-being with time management, and think about the meaning of patient-centredness. Finally, active participation in clinical clerkship longitudinally may provide students with opportunities to learn from their errors.

Approaching the intrinsic exciton physics limit in two-dimensional semiconductor diodes.

Two-dimensional (2D) semiconductors have attracted intense interest for their unique photophysical properties, including large exciton binding energies and strong gate tunability, which arise from their reduced dimensionality1-5. Despite considerable efforts, a disconnect persists between the fundamental photophysics in pristine 2D semiconductors and the practical device performances, which are often plagued by many extrinsic factors, including chemical disorder at the semiconductor-contact interface. Here, by using van der Waals contacts with minimal interfacial disorder, we suppress contact-induced Shockley-Read-Hall recombination and realize nearly intrinsic photophysics-dictated device performance in 2D semiconductor diodes. Using an electrostatic field in a split-gate geometry to independently modulate electron and hole doping in tungsten diselenide diodes, we discover an unusual peak in the short-circuit photocurrent at low charge densities. Time-resolved photoluminescence reveals a substantial decrease of the exciton lifetime from around 800 picoseconds in the charge-neutral regime to around 50 picoseconds at high doping densities owing to increased exciton-charge Auger recombination. Taken together, we show that an exciton-diffusion-limited model well explains the charge-density-dependent short-circuit photocurrent, a result further confirmed by scanning photocurrent microscopy. We thus demonstrate the fundamental role of exciton diffusion and two-body exciton-charge Auger recombination in 2D devices and highlight that the intrinsic photophysics of 2D semiconductors can be used to create more efficient optoelectronic devices.